|
Percentage inhibition against antigen-induced IL-4 production in RBL-2H3 cells at 0 uM concentration
|
Rattus norvegicus
|
0.0
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Antiallergic principles from Alpinia galanga: structural requirements of phenylpropanoids for inhibition of degranulation and release of TNF-alpha and IL-4 in RBL-2H3 cells.
Year : 2003
Volume : 13
Issue : 19
First Page : 3197
Last Page : 3202
Authors : Matsuda H, Morikawa T, Managi H, Yoshikawa M.
Abstract : The 80% aqueous acetone extract of the rhizomes of Alpinia galanga was found to inhibit release of beta-hexosaminidase, as a marker of antigen-IgE-mediated degranulation in RBL-2H3 cells. Nine known phenylpropanoids and p-hydroxybenzaldehyde were isolated from the extract. Among them, 1'S-1'-acetoxychavicol acetate and 1'S-1'-acetoxyeugenol acetate exhibited potent inhibitory activity with IC(50) values of 15 and 19 microM. From the effects of various related compounds, both the 1'- and 4-acetoxyl groups of 1'S-1'-acetoxychavicol acetate and 1'S-1'-acetoxyeugenol acetate were essential for their strong activity, and the 2'-3' double bond enhanced the activity. In addition, 1'S-1'-acetoxychavicol acetate and 1'S-1'-acetoxyeugenol acetate inhibited ear passive cutaneous anaphylaxis reactions in mice and the antigen-IgE-mediated TNF-alpha and IL-4 production, both of which participate in the late phase of type I allergic reactions, in RBL-2H3 cells.
|
Percentage inhibition against antigen-induced IL-4 production in RBL-2H3 cells at 10 uM concentration
|
Rattus norvegicus
|
89.4
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Antiallergic principles from Alpinia galanga: structural requirements of phenylpropanoids for inhibition of degranulation and release of TNF-alpha and IL-4 in RBL-2H3 cells.
Year : 2003
Volume : 13
Issue : 19
First Page : 3197
Last Page : 3202
Authors : Matsuda H, Morikawa T, Managi H, Yoshikawa M.
Abstract : The 80% aqueous acetone extract of the rhizomes of Alpinia galanga was found to inhibit release of beta-hexosaminidase, as a marker of antigen-IgE-mediated degranulation in RBL-2H3 cells. Nine known phenylpropanoids and p-hydroxybenzaldehyde were isolated from the extract. Among them, 1'S-1'-acetoxychavicol acetate and 1'S-1'-acetoxyeugenol acetate exhibited potent inhibitory activity with IC(50) values of 15 and 19 microM. From the effects of various related compounds, both the 1'- and 4-acetoxyl groups of 1'S-1'-acetoxychavicol acetate and 1'S-1'-acetoxyeugenol acetate were essential for their strong activity, and the 2'-3' double bond enhanced the activity. In addition, 1'S-1'-acetoxychavicol acetate and 1'S-1'-acetoxyeugenol acetate inhibited ear passive cutaneous anaphylaxis reactions in mice and the antigen-IgE-mediated TNF-alpha and IL-4 production, both of which participate in the late phase of type I allergic reactions, in RBL-2H3 cells.
|
Percentage inhibition against antigen-induced IL-4 production in RBL-2H3 cells at 3 uM concentration
|
Rattus norvegicus
|
41.6
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Antiallergic principles from Alpinia galanga: structural requirements of phenylpropanoids for inhibition of degranulation and release of TNF-alpha and IL-4 in RBL-2H3 cells.
Year : 2003
Volume : 13
Issue : 19
First Page : 3197
Last Page : 3202
Authors : Matsuda H, Morikawa T, Managi H, Yoshikawa M.
Abstract : The 80% aqueous acetone extract of the rhizomes of Alpinia galanga was found to inhibit release of beta-hexosaminidase, as a marker of antigen-IgE-mediated degranulation in RBL-2H3 cells. Nine known phenylpropanoids and p-hydroxybenzaldehyde were isolated from the extract. Among them, 1'S-1'-acetoxychavicol acetate and 1'S-1'-acetoxyeugenol acetate exhibited potent inhibitory activity with IC(50) values of 15 and 19 microM. From the effects of various related compounds, both the 1'- and 4-acetoxyl groups of 1'S-1'-acetoxychavicol acetate and 1'S-1'-acetoxyeugenol acetate were essential for their strong activity, and the 2'-3' double bond enhanced the activity. In addition, 1'S-1'-acetoxychavicol acetate and 1'S-1'-acetoxyeugenol acetate inhibited ear passive cutaneous anaphylaxis reactions in mice and the antigen-IgE-mediated TNF-alpha and IL-4 production, both of which participate in the late phase of type I allergic reactions, in RBL-2H3 cells.
|
Percentage inhibition against antigen-induced IL-4 production in RBL-2H3 cells at 30 uM concentration
|
Rattus norvegicus
|
99.2
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Antiallergic principles from Alpinia galanga: structural requirements of phenylpropanoids for inhibition of degranulation and release of TNF-alpha and IL-4 in RBL-2H3 cells.
Year : 2003
Volume : 13
Issue : 19
First Page : 3197
Last Page : 3202
Authors : Matsuda H, Morikawa T, Managi H, Yoshikawa M.
Abstract : The 80% aqueous acetone extract of the rhizomes of Alpinia galanga was found to inhibit release of beta-hexosaminidase, as a marker of antigen-IgE-mediated degranulation in RBL-2H3 cells. Nine known phenylpropanoids and p-hydroxybenzaldehyde were isolated from the extract. Among them, 1'S-1'-acetoxychavicol acetate and 1'S-1'-acetoxyeugenol acetate exhibited potent inhibitory activity with IC(50) values of 15 and 19 microM. From the effects of various related compounds, both the 1'- and 4-acetoxyl groups of 1'S-1'-acetoxychavicol acetate and 1'S-1'-acetoxyeugenol acetate were essential for their strong activity, and the 2'-3' double bond enhanced the activity. In addition, 1'S-1'-acetoxychavicol acetate and 1'S-1'-acetoxyeugenol acetate inhibited ear passive cutaneous anaphylaxis reactions in mice and the antigen-IgE-mediated TNF-alpha and IL-4 production, both of which participate in the late phase of type I allergic reactions, in RBL-2H3 cells.
|
Percentage inhibition against antigen-induced TNF-alpha production in RBL-2H3 cells at 0 uM concentration
|
Rattus norvegicus
|
0.0
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Antiallergic principles from Alpinia galanga: structural requirements of phenylpropanoids for inhibition of degranulation and release of TNF-alpha and IL-4 in RBL-2H3 cells.
Year : 2003
Volume : 13
Issue : 19
First Page : 3197
Last Page : 3202
Authors : Matsuda H, Morikawa T, Managi H, Yoshikawa M.
Abstract : The 80% aqueous acetone extract of the rhizomes of Alpinia galanga was found to inhibit release of beta-hexosaminidase, as a marker of antigen-IgE-mediated degranulation in RBL-2H3 cells. Nine known phenylpropanoids and p-hydroxybenzaldehyde were isolated from the extract. Among them, 1'S-1'-acetoxychavicol acetate and 1'S-1'-acetoxyeugenol acetate exhibited potent inhibitory activity with IC(50) values of 15 and 19 microM. From the effects of various related compounds, both the 1'- and 4-acetoxyl groups of 1'S-1'-acetoxychavicol acetate and 1'S-1'-acetoxyeugenol acetate were essential for their strong activity, and the 2'-3' double bond enhanced the activity. In addition, 1'S-1'-acetoxychavicol acetate and 1'S-1'-acetoxyeugenol acetate inhibited ear passive cutaneous anaphylaxis reactions in mice and the antigen-IgE-mediated TNF-alpha and IL-4 production, both of which participate in the late phase of type I allergic reactions, in RBL-2H3 cells.
|
Percentage inhibition against antigen-induced TNF-alpha production in RBL-2H3 cells at 10 uM concentration
|
Rattus norvegicus
|
89.0
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Antiallergic principles from Alpinia galanga: structural requirements of phenylpropanoids for inhibition of degranulation and release of TNF-alpha and IL-4 in RBL-2H3 cells.
Year : 2003
Volume : 13
Issue : 19
First Page : 3197
Last Page : 3202
Authors : Matsuda H, Morikawa T, Managi H, Yoshikawa M.
Abstract : The 80% aqueous acetone extract of the rhizomes of Alpinia galanga was found to inhibit release of beta-hexosaminidase, as a marker of antigen-IgE-mediated degranulation in RBL-2H3 cells. Nine known phenylpropanoids and p-hydroxybenzaldehyde were isolated from the extract. Among them, 1'S-1'-acetoxychavicol acetate and 1'S-1'-acetoxyeugenol acetate exhibited potent inhibitory activity with IC(50) values of 15 and 19 microM. From the effects of various related compounds, both the 1'- and 4-acetoxyl groups of 1'S-1'-acetoxychavicol acetate and 1'S-1'-acetoxyeugenol acetate were essential for their strong activity, and the 2'-3' double bond enhanced the activity. In addition, 1'S-1'-acetoxychavicol acetate and 1'S-1'-acetoxyeugenol acetate inhibited ear passive cutaneous anaphylaxis reactions in mice and the antigen-IgE-mediated TNF-alpha and IL-4 production, both of which participate in the late phase of type I allergic reactions, in RBL-2H3 cells.
|
Percentage inhibition against antigen-induced TNF-alpha production in RBL-2H3 cells at 3 uM concentration
|
Rattus norvegicus
|
25.0
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Antiallergic principles from Alpinia galanga: structural requirements of phenylpropanoids for inhibition of degranulation and release of TNF-alpha and IL-4 in RBL-2H3 cells.
Year : 2003
Volume : 13
Issue : 19
First Page : 3197
Last Page : 3202
Authors : Matsuda H, Morikawa T, Managi H, Yoshikawa M.
Abstract : The 80% aqueous acetone extract of the rhizomes of Alpinia galanga was found to inhibit release of beta-hexosaminidase, as a marker of antigen-IgE-mediated degranulation in RBL-2H3 cells. Nine known phenylpropanoids and p-hydroxybenzaldehyde were isolated from the extract. Among them, 1'S-1'-acetoxychavicol acetate and 1'S-1'-acetoxyeugenol acetate exhibited potent inhibitory activity with IC(50) values of 15 and 19 microM. From the effects of various related compounds, both the 1'- and 4-acetoxyl groups of 1'S-1'-acetoxychavicol acetate and 1'S-1'-acetoxyeugenol acetate were essential for their strong activity, and the 2'-3' double bond enhanced the activity. In addition, 1'S-1'-acetoxychavicol acetate and 1'S-1'-acetoxyeugenol acetate inhibited ear passive cutaneous anaphylaxis reactions in mice and the antigen-IgE-mediated TNF-alpha and IL-4 production, both of which participate in the late phase of type I allergic reactions, in RBL-2H3 cells.
|
Percentage inhibition against antigen-induced TNF-alpha production in RBL-2H3 cells at 30 uM concentration
|
Rattus norvegicus
|
101.3
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Antiallergic principles from Alpinia galanga: structural requirements of phenylpropanoids for inhibition of degranulation and release of TNF-alpha and IL-4 in RBL-2H3 cells.
Year : 2003
Volume : 13
Issue : 19
First Page : 3197
Last Page : 3202
Authors : Matsuda H, Morikawa T, Managi H, Yoshikawa M.
Abstract : The 80% aqueous acetone extract of the rhizomes of Alpinia galanga was found to inhibit release of beta-hexosaminidase, as a marker of antigen-IgE-mediated degranulation in RBL-2H3 cells. Nine known phenylpropanoids and p-hydroxybenzaldehyde were isolated from the extract. Among them, 1'S-1'-acetoxychavicol acetate and 1'S-1'-acetoxyeugenol acetate exhibited potent inhibitory activity with IC(50) values of 15 and 19 microM. From the effects of various related compounds, both the 1'- and 4-acetoxyl groups of 1'S-1'-acetoxychavicol acetate and 1'S-1'-acetoxyeugenol acetate were essential for their strong activity, and the 2'-3' double bond enhanced the activity. In addition, 1'S-1'-acetoxychavicol acetate and 1'S-1'-acetoxyeugenol acetate inhibited ear passive cutaneous anaphylaxis reactions in mice and the antigen-IgE-mediated TNF-alpha and IL-4 production, both of which participate in the late phase of type I allergic reactions, in RBL-2H3 cells.
|
Inhibition of glycogen synthase kinase 3
|
None
|
800.0
nM
|
|
Journal : J. Med. Chem.
Title : Crystal structure of a human cyclin-dependent kinase 6 complex with a flavonol inhibitor, fisetin.
Year : 2005
Volume : 48
Issue : 3
First Page : 737
Last Page : 743
Authors : Lu H, Chang DJ, Baratte B, Meijer L, Schulze-Gahmen U.
Abstract : Cyclin-dependent kinases (CDKs) play a central role in cell cycle control, apoptosis, transcription, and neuronal functions. They are important targets for the design of drugs with antimitotic or antineurodegenerative effects. CDK4 and CDK6 form a subfamily among the CDKs in mammalian cells, as defined by sequence similarities. Compared to CDK2 and CDK5, structural information on CDK4 and CDK6 is sparse. We describe here the crystal structure of human CDK6 in complex with a viral cyclin and a flavonol inhibitor, fisetin. Fisetin binds to the active form of CDK6, forming hydrogen bonds with the side chains of residues in the binding pocket that undergo large conformational changes during CDK activation by cyclin binding. The 4-keto group and the 3-hydroxyl group of fisetin are hydrogen bonded with the backbone in the hinge region between the N-terminal and C-terminal kinase domain, as has been observed for many CDK inhibitors. However, CDK2 and HCK kinase in complex with other flavone inhibitors such as quercetin and flavopiridol showed a different binding mode with the inhibitor rotated by about 180 degrees. The structural information of the CDK6-fisetin complex is correlated with the binding affinities of different flavone inhibitors for CDK6. This complex structure is the first description of an inhibitor complex with a kinase from the CDK4/6 subfamily and can provide a basis for selecting and designing inhibitor compounds with higher affinities and specificities.
|
Inhibition of FabG in presence of NADPH
|
Plasmodium falciparum
|
800.0
nM
|
|
Journal : J. Med. Chem.
Title : Inhibition of Plasmodium falciparum fatty acid biosynthesis: evaluation of FabG, FabZ, and FabI as drug targets for flavonoids.
Year : 2006
Volume : 49
Issue : 11
First Page : 3345
Last Page : 3353
Authors : Tasdemir D, Lack G, Brun R, Rüedi P, Scapozza L, Perozzo R.
Abstract : After the discovery of a potent natural flavonoid glucoside as a potent inhibitor of FabI, a large flavonoid library was screened against three important enzymes (i.e., FabG, FabZ, and FabI) involved in the fatty acid biosynthesis of P. falciparum. Although flavones with a simple hydroxylation pattern (compounds 4-9) showed moderate inhibitory activity toward the enzymes tested (IC50 10-100 microM), the more complex flavonoids (12-16) exhibited strong activity toward all three enzymes (IC50 0.5-8 microM). Isoflavonoids 26-28 showed moderate (IC50 7-30 microM) but selective activity against FabZ. The most active compounds were C-3 gallic acid esters of catechins (32, 33, 37, 38), which are strong inhibitors of all three enzymes (IC50 0.2-1.1 microM). Kinetic analysis using luteolin (12) and (-)-catechin gallate (37) as model compounds revealed that FabG was inhibited in a noncompetitive manner. FabZ was inhibited competitively, whereas both compounds behaved as tight-binding noncompetitive inhibitors of FabI. In addition, these polyphenols showed in vitro activity against chloroquine-sensitive (NF54) and -resistant (K1) P. falciparum strains in the low to submicromolar range.
|
Peroxynitrite scavenging activity assessed as inhibition of DHR oxidation
|
None
|
300.0
nM
|
|
Journal : Bioorg. Med. Chem.
Title : 2-Styrylchromones: novel strong scavengers of reactive oxygen and nitrogen species.
Year : 2007
Volume : 15
Issue : 18
First Page : 6027
Last Page : 6036
Authors : Gomes A, Fernandes E, Silva AM, Santos CM, Pinto DC, Cavaleiro JA, Lima JL.
Abstract : 2-Styrylchromones are a small group of naturally occurring chromones, vinylogues of flavones (2-phenylchromones). Natural and synthetic 2-styrylchromones have been tested in different biological systems, showing activities with potential therapeutic applications. In particular, the potential and hitherto understudied antioxidant behavior of these compounds has been raised as a matter of interest. Thus the present work consisted in the study of the in vitro scavenging activities for reactive oxygen species (ROS) and reactive nitrogen species (RNS) of various 2-styrylchromone derivatives and structurally similar flavonoids. Some of the studied 2-styrylchromones proved to be extremely efficient scavengers of the different ROS and RNS, showing, in some cases, IC(50)s under 1 microM. The hydroxylation pattern of 2-styrylchromones, especially in the B-ring but also in the A ring, modulates the activity of these compounds, the catecholic derivatives being the most effective scavengers. The styryl pattern also contributes to their observed outstanding antioxidant activity. In conclusion, the scavenging activities for ROS/RNS of 2-styrylchromone derivatives, here shown for the first time, provide novel and most promising compounds to be applied as antioxidants.
|
Peroxynitrite scavenging activity assessed as inhibition of DHR oxidation in presence of NaHCo3
|
None
|
640.0
nM
|
|
Journal : Bioorg. Med. Chem.
Title : 2-Styrylchromones: novel strong scavengers of reactive oxygen and nitrogen species.
Year : 2007
Volume : 15
Issue : 18
First Page : 6027
Last Page : 6036
Authors : Gomes A, Fernandes E, Silva AM, Santos CM, Pinto DC, Cavaleiro JA, Lima JL.
Abstract : 2-Styrylchromones are a small group of naturally occurring chromones, vinylogues of flavones (2-phenylchromones). Natural and synthetic 2-styrylchromones have been tested in different biological systems, showing activities with potential therapeutic applications. In particular, the potential and hitherto understudied antioxidant behavior of these compounds has been raised as a matter of interest. Thus the present work consisted in the study of the in vitro scavenging activities for reactive oxygen species (ROS) and reactive nitrogen species (RNS) of various 2-styrylchromone derivatives and structurally similar flavonoids. Some of the studied 2-styrylchromones proved to be extremely efficient scavengers of the different ROS and RNS, showing, in some cases, IC(50)s under 1 microM. The hydroxylation pattern of 2-styrylchromones, especially in the B-ring but also in the A ring, modulates the activity of these compounds, the catecholic derivatives being the most effective scavengers. The styryl pattern also contributes to their observed outstanding antioxidant activity. In conclusion, the scavenging activities for ROS/RNS of 2-styrylchromone derivatives, here shown for the first time, provide novel and most promising compounds to be applied as antioxidants.
|
Inhibition of COX2 in I1-10-stimulated bone marrow derived mast cells
|
None
|
80.0
%
|
|
Journal : J. Nat. Prod.
Title : Screening of ubiquitous plant constituents for COX-2 inhibition with a scintillation proximity based assay.
Year : 2002
Volume : 65
Issue : 11
First Page : 1517
Last Page : 1521
Authors : Huss U, Ringbom T, Perera P, Bohlin L, Vasänge M.
Abstract : A rapid semi-homogeneous cyclooxygenase-2 (COX-2) enzymatic assay using scintillation proximity assay (SPA) technology was developed, and 49 ubiquitous plant secondary metabolites were screened for inhibition of COX-2-catalyzed prostaglandin E(2) (PGE(2)) biosynthesis. Assay conditions were optimized with respect to reaction time, amount of antibody, radiolabeled PGE(2), and SPA beads, and the kinetic parameter, K(m), was estimated. The assay was validated with two natural triterpenoids, ursolic and oleanolic acid, known to inhibit COX-2, as well as with four synthetic COX inhibitors, NS-398, rofecoxib, indomethacin, and aspirin. Plant metabolites of different biosynthetic origin representing several substance classes, including alkaloids, anthraquinones, flavonoids, phenylpropanes, steroids, and terpenes, were screened for inhibition of COX-2-catalyzed PGE(2) production. Of these 49 plant metabolites, eugenol, pyrogallol, and cinnamaldehyde (with IC(50) values of 129, 144, and 245 microM, respectively) were found to inhibit COX-2. This study showed that a COX-2-catalyzed PGE(2) assay using SPA is suitable for screening natural compounds with respect to COX-2 inhibition.
|
Inhibition of COX2 at 100 uM by scintillation proximity assay
|
None
|
30.0
%
|
|
Journal : J. Nat. Prod.
Title : Screening of ubiquitous plant constituents for COX-2 inhibition with a scintillation proximity based assay.
Year : 2002
Volume : 65
Issue : 11
First Page : 1517
Last Page : 1521
Authors : Huss U, Ringbom T, Perera P, Bohlin L, Vasänge M.
Abstract : A rapid semi-homogeneous cyclooxygenase-2 (COX-2) enzymatic assay using scintillation proximity assay (SPA) technology was developed, and 49 ubiquitous plant secondary metabolites were screened for inhibition of COX-2-catalyzed prostaglandin E(2) (PGE(2)) biosynthesis. Assay conditions were optimized with respect to reaction time, amount of antibody, radiolabeled PGE(2), and SPA beads, and the kinetic parameter, K(m), was estimated. The assay was validated with two natural triterpenoids, ursolic and oleanolic acid, known to inhibit COX-2, as well as with four synthetic COX inhibitors, NS-398, rofecoxib, indomethacin, and aspirin. Plant metabolites of different biosynthetic origin representing several substance classes, including alkaloids, anthraquinones, flavonoids, phenylpropanes, steroids, and terpenes, were screened for inhibition of COX-2-catalyzed PGE(2) production. Of these 49 plant metabolites, eugenol, pyrogallol, and cinnamaldehyde (with IC(50) values of 129, 144, and 245 microM, respectively) were found to inhibit COX-2. This study showed that a COX-2-catalyzed PGE(2) assay using SPA is suitable for screening natural compounds with respect to COX-2 inhibition.
|
Inhibition of COX2
|
None
|
100.0
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Screening of ubiquitous plant constituents for COX-2 inhibition with a scintillation proximity based assay.
Year : 2002
Volume : 65
Issue : 11
First Page : 1517
Last Page : 1521
Authors : Huss U, Ringbom T, Perera P, Bohlin L, Vasänge M.
Abstract : A rapid semi-homogeneous cyclooxygenase-2 (COX-2) enzymatic assay using scintillation proximity assay (SPA) technology was developed, and 49 ubiquitous plant secondary metabolites were screened for inhibition of COX-2-catalyzed prostaglandin E(2) (PGE(2)) biosynthesis. Assay conditions were optimized with respect to reaction time, amount of antibody, radiolabeled PGE(2), and SPA beads, and the kinetic parameter, K(m), was estimated. The assay was validated with two natural triterpenoids, ursolic and oleanolic acid, known to inhibit COX-2, as well as with four synthetic COX inhibitors, NS-398, rofecoxib, indomethacin, and aspirin. Plant metabolites of different biosynthetic origin representing several substance classes, including alkaloids, anthraquinones, flavonoids, phenylpropanes, steroids, and terpenes, were screened for inhibition of COX-2-catalyzed PGE(2) production. Of these 49 plant metabolites, eugenol, pyrogallol, and cinnamaldehyde (with IC(50) values of 129, 144, and 245 microM, respectively) were found to inhibit COX-2. This study showed that a COX-2-catalyzed PGE(2) assay using SPA is suitable for screening natural compounds with respect to COX-2 inhibition.
|
Inhibition of COX2 in LPS-stimulated bone marrow derived mast cells
|
None
|
2.5
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Screening of ubiquitous plant constituents for COX-2 inhibition with a scintillation proximity based assay.
Year : 2002
Volume : 65
Issue : 11
First Page : 1517
Last Page : 1521
Authors : Huss U, Ringbom T, Perera P, Bohlin L, Vasänge M.
Abstract : A rapid semi-homogeneous cyclooxygenase-2 (COX-2) enzymatic assay using scintillation proximity assay (SPA) technology was developed, and 49 ubiquitous plant secondary metabolites were screened for inhibition of COX-2-catalyzed prostaglandin E(2) (PGE(2)) biosynthesis. Assay conditions were optimized with respect to reaction time, amount of antibody, radiolabeled PGE(2), and SPA beads, and the kinetic parameter, K(m), was estimated. The assay was validated with two natural triterpenoids, ursolic and oleanolic acid, known to inhibit COX-2, as well as with four synthetic COX inhibitors, NS-398, rofecoxib, indomethacin, and aspirin. Plant metabolites of different biosynthetic origin representing several substance classes, including alkaloids, anthraquinones, flavonoids, phenylpropanes, steroids, and terpenes, were screened for inhibition of COX-2-catalyzed PGE(2) production. Of these 49 plant metabolites, eugenol, pyrogallol, and cinnamaldehyde (with IC(50) values of 129, 144, and 245 microM, respectively) were found to inhibit COX-2. This study showed that a COX-2-catalyzed PGE(2) assay using SPA is suitable for screening natural compounds with respect to COX-2 inhibition.
|
Inhibition of bovine thymus p56LCK-catalyzed phosphorylation of angiotensin 1 by SDS-PAGE
|
Bos taurus
|
10.0
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Synthesis and evaluation of hydroxylated flavones and related compounds as potential inhibitors of the protein-tyrosine kinase p56lck.
Year : 1991
Volume : 54
Issue : 5
First Page : 1345
Last Page : 1352
Authors : Cushman M, Nagarathnam D, Geahlen RL.
Abstract : An array of hydroxylated flavones and related compounds was synthesized and evaluated for inhibition of the in vitro protein-tyrosine kinase activity of p56lck, an enzyme that is thought to play a key role in mediating signal transduction from the CD4 receptor during lymphocyte activation. In general, the most active compounds had hydroxyl groups on both the A and C rings. At least two hydroxyl groups were required for good inhibitory activity, and the relative positions of these groups played an important role in determining potency. Compounds without hydroxyl groups were inactive as inhibitors.
|
Inhibition of bovine thymus p56-LCK protein tyrosine kinase activity
|
Bos taurus
|
4.0
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Flavonoids from Koelreuteria henryi and other sources as protein-tyrosine kinase inhibitors.
Year : 1993
Volume : 56
Issue : 6
First Page : 967
Last Page : 969
Authors : Abou-Shoer M, Ma GE, Li XH, Koonchanok NM, Geahlen RL, Chang CJ.
Abstract : The EtOH extract of Koelreuteria henryi was investigated in a search for natural products with potential protein-tryrosine kinase (PTK) inhibitory activity. The PTK inhibitory activity of the crude fractions was determined by measuring their inhibition of p56lck partially purified from bovine thymus using angiotensin I as a substrate. Analysis of those fractions that exhibited significant activity led to the isolation of kaempferol and quercetin, in addition to two kaempferol glycosides, kaempferol-O3-alpha-rhamnopyranoside [1] and kaempferol-O3-alpha-arabinopyranoside [2]. This study represents the first report on the isolation of flavonols and their PTK inhibitory activities from the genus Koelreuteria. Eight other flavonoids were also examined to study the role of the hydroxy groups on the B ring on PTK inhibitory activity.
|
Inhibition of Saccharomyces cerevisiae fatty acid synthase
|
Saccharomyces cerevisiae
|
9.0
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Fatty acid synthase inhibitors from plants: isolation, structure elucidation, and SAR studies.
Year : 2002
Volume : 65
Issue : 12
First Page : 1909
Last Page : 1914
Authors : Li XC, Joshi AS, ElSohly HN, Khan SI, Jacob MR, Zhang Z, Khan IA, Ferreira D, Walker LA, Broedel SE, Raulli RE, Cihlar RL.
Abstract : Fatty acid synthase (FAS) has been identified as a potential antifungal target. FAS prepared from Saccharomyces cerevisiae was employed for bioactivity-guided fractionation of Chlorophora tinctoria,Paspalum conjugatum, Symphonia globulifera, Buchenavia parviflora, and Miconia pilgeriana. Thirteen compounds (1-13), including three new natural products (1, 4, 12), were isolated and their structures identified by spectroscopic interpretation. They represented five chemotypes, namely, isoflavones, flavones, biflavonoids, hydrolyzable tannin-related derivatives, and triterpenoids. 3'-Formylgenistein (1) and ellagic acid 4-O-alpha-l-rhamnopyranoside (9) were the most potent compounds against FAS, with IC(50) values of 2.3 and 7.5 microg/mL, respectively. Furthermore, 43 (14-56) analogues of the five chemotypes from our natural product repository and commercial sources were tested for their FAS inhibitory activity. Structure-activity relationships for some chemotypes were investigated. All these compounds were further evaluated for antifungal activity against Candida albicans and Cryptococcus neoformans. Although there were several antifungal compounds in the set, correlation between the FAS inhibitory activity and antifungal activity could not be defined.
|
Antifungal activity against Candida albicans ATCC 90028
|
Candida albicans
|
50.0
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Fatty acid synthase inhibitors from plants: isolation, structure elucidation, and SAR studies.
Year : 2002
Volume : 65
Issue : 12
First Page : 1909
Last Page : 1914
Authors : Li XC, Joshi AS, ElSohly HN, Khan SI, Jacob MR, Zhang Z, Khan IA, Ferreira D, Walker LA, Broedel SE, Raulli RE, Cihlar RL.
Abstract : Fatty acid synthase (FAS) has been identified as a potential antifungal target. FAS prepared from Saccharomyces cerevisiae was employed for bioactivity-guided fractionation of Chlorophora tinctoria,Paspalum conjugatum, Symphonia globulifera, Buchenavia parviflora, and Miconia pilgeriana. Thirteen compounds (1-13), including three new natural products (1, 4, 12), were isolated and their structures identified by spectroscopic interpretation. They represented five chemotypes, namely, isoflavones, flavones, biflavonoids, hydrolyzable tannin-related derivatives, and triterpenoids. 3'-Formylgenistein (1) and ellagic acid 4-O-alpha-l-rhamnopyranoside (9) were the most potent compounds against FAS, with IC(50) values of 2.3 and 7.5 microg/mL, respectively. Furthermore, 43 (14-56) analogues of the five chemotypes from our natural product repository and commercial sources were tested for their FAS inhibitory activity. Structure-activity relationships for some chemotypes were investigated. All these compounds were further evaluated for antifungal activity against Candida albicans and Cryptococcus neoformans. Although there were several antifungal compounds in the set, correlation between the FAS inhibitory activity and antifungal activity could not be defined.
|
Antifungal activity against Cryptococcus neoformans ATCC 90113
|
Cryptococcus neoformans
|
50.0
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Fatty acid synthase inhibitors from plants: isolation, structure elucidation, and SAR studies.
Year : 2002
Volume : 65
Issue : 12
First Page : 1909
Last Page : 1914
Authors : Li XC, Joshi AS, ElSohly HN, Khan SI, Jacob MR, Zhang Z, Khan IA, Ferreira D, Walker LA, Broedel SE, Raulli RE, Cihlar RL.
Abstract : Fatty acid synthase (FAS) has been identified as a potential antifungal target. FAS prepared from Saccharomyces cerevisiae was employed for bioactivity-guided fractionation of Chlorophora tinctoria,Paspalum conjugatum, Symphonia globulifera, Buchenavia parviflora, and Miconia pilgeriana. Thirteen compounds (1-13), including three new natural products (1, 4, 12), were isolated and their structures identified by spectroscopic interpretation. They represented five chemotypes, namely, isoflavones, flavones, biflavonoids, hydrolyzable tannin-related derivatives, and triterpenoids. 3'-Formylgenistein (1) and ellagic acid 4-O-alpha-l-rhamnopyranoside (9) were the most potent compounds against FAS, with IC(50) values of 2.3 and 7.5 microg/mL, respectively. Furthermore, 43 (14-56) analogues of the five chemotypes from our natural product repository and commercial sources were tested for their FAS inhibitory activity. Structure-activity relationships for some chemotypes were investigated. All these compounds were further evaluated for antifungal activity against Candida albicans and Cryptococcus neoformans. Although there were several antifungal compounds in the set, correlation between the FAS inhibitory activity and antifungal activity could not be defined.
|
Inhibition of p56 lck
|
None
|
10.0
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Protein-tyrosine kinase inhibition: mechanism-based discovery of antitumor agents.
Year : 1992
Volume : 55
Issue : 11
First Page : 1529
Last Page : 1560
Authors : Chang CJ, Geahlen RL.
Abstract : Protein-tyrosine kinases (PTKs) have been shown to induce the cascade of altered cell parameters characteristic of transformed cells. This proposition provides an important rationale for the discovery of potential antitumor agents from natural sources on the basis of inhibition of PTK activity. Numerous naturally occurring and synthetic analogues of PTK inhibitors were systematically evaluated in this review based on their structure-activity relationships and potential antitumor efficacy.
|
Cytotoxicity against human HL60 cells after 3 days by MTT assay
|
Homo sapiens
|
10.0
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Chemical constituents from Lippia sidoides and cytotoxic activity.
Year : 2001
Volume : 64
Issue : 6
First Page : 792
Last Page : 795
Authors : Costa SM, Lemos TL, Pessoa OD, Pessoa C, Montenegro RC, Braz-Filho R.
Abstract : Eleven known compounds and a new prenylated naphthoquinone, lippsidoquinone (13), were isolated from ethanol extracts of Lippia sidoides. Their structures were established by a combination of 1D and 2D NMR, IR, and EIMS spectral data analysis. The cytotoxic properties of compounds 3--13 were evaluated against HL60, SW1573, and CEM cell lines. Only tectol (6) and lippsidoquinone (13) exhibited significant activity against human leukemia cell lines HL60 and CEM.
|
Cytotoxicity against human SW1573 cells after 3 days by MTT assay
|
Homo sapiens
|
10.0
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Chemical constituents from Lippia sidoides and cytotoxic activity.
Year : 2001
Volume : 64
Issue : 6
First Page : 792
Last Page : 795
Authors : Costa SM, Lemos TL, Pessoa OD, Pessoa C, Montenegro RC, Braz-Filho R.
Abstract : Eleven known compounds and a new prenylated naphthoquinone, lippsidoquinone (13), were isolated from ethanol extracts of Lippia sidoides. Their structures were established by a combination of 1D and 2D NMR, IR, and EIMS spectral data analysis. The cytotoxic properties of compounds 3--13 were evaluated against HL60, SW1573, and CEM cell lines. Only tectol (6) and lippsidoquinone (13) exhibited significant activity against human leukemia cell lines HL60 and CEM.
|
Cytotoxicity against human CEM cells after 3 days by MTT assay
|
Homo sapiens
|
10.0
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Chemical constituents from Lippia sidoides and cytotoxic activity.
Year : 2001
Volume : 64
Issue : 6
First Page : 792
Last Page : 795
Authors : Costa SM, Lemos TL, Pessoa OD, Pessoa C, Montenegro RC, Braz-Filho R.
Abstract : Eleven known compounds and a new prenylated naphthoquinone, lippsidoquinone (13), were isolated from ethanol extracts of Lippia sidoides. Their structures were established by a combination of 1D and 2D NMR, IR, and EIMS spectral data analysis. The cytotoxic properties of compounds 3--13 were evaluated against HL60, SW1573, and CEM cell lines. Only tectol (6) and lippsidoquinone (13) exhibited significant activity against human leukemia cell lines HL60 and CEM.
|
Antioxidant activity assessed as DPPH free radical scavenging activity
|
None
|
7.2
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Acylated flavonol glycosides from the flower of Inula britannica.
Year : 2000
Volume : 63
Issue : 1
First Page : 34
Last Page : 36
Authors : Park EJ, Kim Y, Kim J.
Abstract : Three new acylated flavonol glycosides, patuletin 7-O-(6' '-isobutyryl)glucoside (1), patuletin 7-O-[6' '-(2-methylbutyryl)]glucoside (2), and patuletin 7-O-(6' '-isovaleryl)glucoside (3), were isolated from the n-BuOH extract of Inula britannica flowers by bioassay-guided fractionation, together with other known flavonoids. The structures were elucidated by 1D and 2D NMR, FABMS, and other spectral analyses. The eight flavonoids, including new compounds (1-3), patulitrin (7), nepitrin (8), axillarin (10), patuletin (11), and luteolin (12), showed profound antioxidant activity in DPPH assay and cytochrome-c reduction assay using HL-60 cell culture system.
|
Antioxidant activity in human HL60 cells assessed as reduction of cytochrome-c release
|
Homo sapiens
|
12.1
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Acylated flavonol glycosides from the flower of Inula britannica.
Year : 2000
Volume : 63
Issue : 1
First Page : 34
Last Page : 36
Authors : Park EJ, Kim Y, Kim J.
Abstract : Three new acylated flavonol glycosides, patuletin 7-O-(6' '-isobutyryl)glucoside (1), patuletin 7-O-[6' '-(2-methylbutyryl)]glucoside (2), and patuletin 7-O-(6' '-isovaleryl)glucoside (3), were isolated from the n-BuOH extract of Inula britannica flowers by bioassay-guided fractionation, together with other known flavonoids. The structures were elucidated by 1D and 2D NMR, FABMS, and other spectral analyses. The eight flavonoids, including new compounds (1-3), patulitrin (7), nepitrin (8), axillarin (10), patuletin (11), and luteolin (12), showed profound antioxidant activity in DPPH assay and cytochrome-c reduction assay using HL-60 cell culture system.
|
Inhibition of xanthine oxidase assessed as decrease in uric acid production by spectrophotometry
|
None
|
550.0
nM
|
|
Journal : J. Nat. Prod.
Title : Structure-activity relationship and classification of flavonoids as inhibitors of xanthine oxidase and superoxide scavengers.
Year : 1998
Volume : 61
Issue : 1
First Page : 71
Last Page : 76
Authors : Cos P, Ying L, Calomme M, Hu JP, Cimanga K, Van Poel B, Pieters L, Vlietinck AJ, Vanden Berghe D.
Abstract : The structure-activity relationship of flavonoids as inhibitors of xanthine oxidase and as scavengers of the superoxide radical, produced by the action of the enzyme xanthine oxidase, was investigated. The hydroxyl groups at C-5 and C-7 and the double bond between C-2 and C-3 were essential for a high inhibitory activity on xanthine oxidase. Flavones showed slightly higher inhibitory activity than flavonols. All flavonoid derivatives except isorhamnetin (30) were less active than the original compounds. For a high superoxide scavenging activity on the other hand, a hydroxyl group at C-3' in ring B and at C-3 were essential. According to their effect on xanthine oxidase and as superoxide scavengers, the flavonoids could be classified into six groups: superoxide scavengers without inhibitory activity on xanthine oxidase (category A), xanthine oxidase inhibitors without any additional superoxide scavenging activity (category B), xanthine oxidase inhibitors with an additional superoxide scavenging activity (category C), xanthine oxidase inhibitors with an additional pro-oxidant effect on the production of superoxide (category D), flavonoids with a marginal effect on xanthine oxidase but with a prooxidant effect on the production of superoxide (category E), and finally, flavonoids with no effect on xanthine oxidase or superoxide (category F).
|
Inhibition of COX2 at 2.5 ug/mL
|
None
|
80.0
%
|
|
Journal : J. Nat. Prod.
Title : Expanding the ChemGPS chemical space with natural products.
Year : 2005
Volume : 68
Issue : 7
First Page : 985
Last Page : 991
Authors : Larsson J, Gottfries J, Bohlin L, Backlund A.
Abstract : Recently various attempts have been made to increase the efficacy and precision of chemical libraries used in high-throughput screening (HTS) drug discovery approaches. One such approach is ChemGPS, which provides a defined chemical space for prescreening evaluation of chemical compound properties or virtual dereplication. In the present study, ChemGPS has been applied to a set of natural products shown to exhibit cyclooxygenase-1 and/or -2 (COX-1/2) inhibition. With the purpose of defining chemical properties and linking these to the observed mode of enzyme inhibition, this resulted in two lines of reasoning. On one hand several specific features of these compounds have been identified and discussed. Overall COX inhibition was frequently correlated with the presence of at least one ring in the structure, fragments exhibiting structural rigidity, and a relatively large molecular size. The concept "size" includes several parameters, e.g., molecular volume, weight, and number of bonds. On the other hand, and possibly even more important, was the unexpected finding that the natural products studied to a large extent fell outside the defined ChemGPS chemical space. Therefore, we also propose an expanded space for natural products: ChemGPS-NP.
|
Inhibition of COX1 at 2.5 ug/mL
|
None
|
75.0
%
|
|
Journal : J. Nat. Prod.
Title : Expanding the ChemGPS chemical space with natural products.
Year : 2005
Volume : 68
Issue : 7
First Page : 985
Last Page : 991
Authors : Larsson J, Gottfries J, Bohlin L, Backlund A.
Abstract : Recently various attempts have been made to increase the efficacy and precision of chemical libraries used in high-throughput screening (HTS) drug discovery approaches. One such approach is ChemGPS, which provides a defined chemical space for prescreening evaluation of chemical compound properties or virtual dereplication. In the present study, ChemGPS has been applied to a set of natural products shown to exhibit cyclooxygenase-1 and/or -2 (COX-1/2) inhibition. With the purpose of defining chemical properties and linking these to the observed mode of enzyme inhibition, this resulted in two lines of reasoning. On one hand several specific features of these compounds have been identified and discussed. Overall COX inhibition was frequently correlated with the presence of at least one ring in the structure, fragments exhibiting structural rigidity, and a relatively large molecular size. The concept "size" includes several parameters, e.g., molecular volume, weight, and number of bonds. On the other hand, and possibly even more important, was the unexpected finding that the natural products studied to a large extent fell outside the defined ChemGPS chemical space. Therefore, we also propose an expanded space for natural products: ChemGPS-NP.
|
Inhibition of human salivary alpha-amylase
|
Homo sapiens
|
88.8
%
|
|
Journal : J. Med. Chem.
Title : Flavonoids for controlling starch digestion: structural requirements for inhibiting human alpha-amylase.
Year : 2008
Volume : 51
Issue : 12
First Page : 3555
Last Page : 3561
Authors : Lo Piparo E, Scheib H, Frei N, Williamson G, Grigorov M, Chou CJ.
Abstract : In this study we investigated the structural requirements for inhibition of human salivary alpha-amylase by flavonoids. Four flavonols and three flavones, out of the 19 flavonoids tested, exhibited IC50 values less than 100 microM against human salivary alpha-amylase activity. Structure-activity relationships of these inhibitors by computational ligand docking showed that the inhibitory activity of flavonols and flavones depends on (i) hydrogen bonds between the hydroxyl groups of the polyphenol ligands and the catalytic residues of the binding site and (ii) formation of a conjugated pi-system that stabilizes the interaction with the active site. Our findings show that certain naturally occurring flavonoids act as inhibitors of human alpha-amylase, which makes them promising candidates for controlling the digestion of starch and postprandial glycemia.
|
Inhibition of theophylline-stimulated melanogenesis in mouse B16-4A5 cells at 30 uM after 72 hrs
|
Mus musculus
|
76.7
%
|
|
Journal : Bioorg. Med. Chem.
Title : Melanogenesis inhibitors from the desert plant Anastatica hierochuntica in B16 melanoma cells.
Year : 2010
Volume : 18
Issue : 6
First Page : 2337
Last Page : 2345
Authors : Nakashima S, Matsuda H, Oda Y, Nakamura S, Xu F, Yoshikawa M.
Abstract : The methanolic extract from the whole plants of Anastatica hierochuntica, an Egyptian herbal medicine, was found to inhibit melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells. Among the constituents isolated, anastatin A, silybin A, isosilybins A and B, eriodictyol, luteolin, kaempferol, quercetin, hierochins A and B, (2R,3S)-2,3-dihydro-2-(3,4-dimethoxyphenyl)-3-hydroxymethyl-5-(2-formylvinyl)-7-hydroxybenzofuran, (+)-dehydrodiconiferyl alcohol, (+)-balanophonin, 1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-hydroxy-1-propenyl]-2-methoxyphenoxy}-1,3-propanediol, and 3,4-dihydroxybenzaldehyde substantially inhibited melanogenesis with IC(50) values of 6.1-32 microM. With regard to the mechanism of action of silybins and isosilybins, the inhibition of tyrosinase activity suggested to be important. In addition, isosilybins A and B inhibited the mRNA expression of TRP-2, but silybins A and B oppositely enhanced the mRNA expression of tyrosinase and TRP-1 and -2 at 10 and/or 30 microM, and the inhibition of phosphorylation of extracellular signal-regulated kinases (ERK1/2) is involved in the enhanced expression of mRNA, at least in part, similar to that of PD98059.
|
Inhibition of theophylline-stimulated melanogenesis in mouse B16-4A5 cells at 10 uM after 72 hrs
|
Mus musculus
|
38.1
%
|
|
Journal : Bioorg. Med. Chem.
Title : Melanogenesis inhibitors from the desert plant Anastatica hierochuntica in B16 melanoma cells.
Year : 2010
Volume : 18
Issue : 6
First Page : 2337
Last Page : 2345
Authors : Nakashima S, Matsuda H, Oda Y, Nakamura S, Xu F, Yoshikawa M.
Abstract : The methanolic extract from the whole plants of Anastatica hierochuntica, an Egyptian herbal medicine, was found to inhibit melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells. Among the constituents isolated, anastatin A, silybin A, isosilybins A and B, eriodictyol, luteolin, kaempferol, quercetin, hierochins A and B, (2R,3S)-2,3-dihydro-2-(3,4-dimethoxyphenyl)-3-hydroxymethyl-5-(2-formylvinyl)-7-hydroxybenzofuran, (+)-dehydrodiconiferyl alcohol, (+)-balanophonin, 1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-hydroxy-1-propenyl]-2-methoxyphenoxy}-1,3-propanediol, and 3,4-dihydroxybenzaldehyde substantially inhibited melanogenesis with IC(50) values of 6.1-32 microM. With regard to the mechanism of action of silybins and isosilybins, the inhibition of tyrosinase activity suggested to be important. In addition, isosilybins A and B inhibited the mRNA expression of TRP-2, but silybins A and B oppositely enhanced the mRNA expression of tyrosinase and TRP-1 and -2 at 10 and/or 30 microM, and the inhibition of phosphorylation of extracellular signal-regulated kinases (ERK1/2) is involved in the enhanced expression of mRNA, at least in part, similar to that of PD98059.
|
Inhibition of theophylline-stimulated melanogenesis in mouse B16-4A5 cells at 3 uM after 72 hrs
|
Mus musculus
|
13.5
%
|
|
Journal : Bioorg. Med. Chem.
Title : Melanogenesis inhibitors from the desert plant Anastatica hierochuntica in B16 melanoma cells.
Year : 2010
Volume : 18
Issue : 6
First Page : 2337
Last Page : 2345
Authors : Nakashima S, Matsuda H, Oda Y, Nakamura S, Xu F, Yoshikawa M.
Abstract : The methanolic extract from the whole plants of Anastatica hierochuntica, an Egyptian herbal medicine, was found to inhibit melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells. Among the constituents isolated, anastatin A, silybin A, isosilybins A and B, eriodictyol, luteolin, kaempferol, quercetin, hierochins A and B, (2R,3S)-2,3-dihydro-2-(3,4-dimethoxyphenyl)-3-hydroxymethyl-5-(2-formylvinyl)-7-hydroxybenzofuran, (+)-dehydrodiconiferyl alcohol, (+)-balanophonin, 1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-hydroxy-1-propenyl]-2-methoxyphenoxy}-1,3-propanediol, and 3,4-dihydroxybenzaldehyde substantially inhibited melanogenesis with IC(50) values of 6.1-32 microM. With regard to the mechanism of action of silybins and isosilybins, the inhibition of tyrosinase activity suggested to be important. In addition, isosilybins A and B inhibited the mRNA expression of TRP-2, but silybins A and B oppositely enhanced the mRNA expression of tyrosinase and TRP-1 and -2 at 10 and/or 30 microM, and the inhibition of phosphorylation of extracellular signal-regulated kinases (ERK1/2) is involved in the enhanced expression of mRNA, at least in part, similar to that of PD98059.
|
Inhibition of theophylline-stimulated melanogenesis in mouse B16-4A5 cells at 1 uM after 72 hrs
|
Mus musculus
|
6.2
%
|
|
Journal : Bioorg. Med. Chem.
Title : Melanogenesis inhibitors from the desert plant Anastatica hierochuntica in B16 melanoma cells.
Year : 2010
Volume : 18
Issue : 6
First Page : 2337
Last Page : 2345
Authors : Nakashima S, Matsuda H, Oda Y, Nakamura S, Xu F, Yoshikawa M.
Abstract : The methanolic extract from the whole plants of Anastatica hierochuntica, an Egyptian herbal medicine, was found to inhibit melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells. Among the constituents isolated, anastatin A, silybin A, isosilybins A and B, eriodictyol, luteolin, kaempferol, quercetin, hierochins A and B, (2R,3S)-2,3-dihydro-2-(3,4-dimethoxyphenyl)-3-hydroxymethyl-5-(2-formylvinyl)-7-hydroxybenzofuran, (+)-dehydrodiconiferyl alcohol, (+)-balanophonin, 1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-hydroxy-1-propenyl]-2-methoxyphenoxy}-1,3-propanediol, and 3,4-dihydroxybenzaldehyde substantially inhibited melanogenesis with IC(50) values of 6.1-32 microM. With regard to the mechanism of action of silybins and isosilybins, the inhibition of tyrosinase activity suggested to be important. In addition, isosilybins A and B inhibited the mRNA expression of TRP-2, but silybins A and B oppositely enhanced the mRNA expression of tyrosinase and TRP-1 and -2 at 10 and/or 30 microM, and the inhibition of phosphorylation of extracellular signal-regulated kinases (ERK1/2) is involved in the enhanced expression of mRNA, at least in part, similar to that of PD98059.
|
Toxicity in mouse B16-4A5 cells assessed as inhibition of cell proliferation at 1 uM in presence of 1 mM theophylline after 72 hrs by WST8 dye reduction assay
|
Mus musculus
|
-4.8
%
|
|
Journal : Bioorg. Med. Chem.
Title : Melanogenesis inhibitors from the desert plant Anastatica hierochuntica in B16 melanoma cells.
Year : 2010
Volume : 18
Issue : 6
First Page : 2337
Last Page : 2345
Authors : Nakashima S, Matsuda H, Oda Y, Nakamura S, Xu F, Yoshikawa M.
Abstract : The methanolic extract from the whole plants of Anastatica hierochuntica, an Egyptian herbal medicine, was found to inhibit melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells. Among the constituents isolated, anastatin A, silybin A, isosilybins A and B, eriodictyol, luteolin, kaempferol, quercetin, hierochins A and B, (2R,3S)-2,3-dihydro-2-(3,4-dimethoxyphenyl)-3-hydroxymethyl-5-(2-formylvinyl)-7-hydroxybenzofuran, (+)-dehydrodiconiferyl alcohol, (+)-balanophonin, 1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-hydroxy-1-propenyl]-2-methoxyphenoxy}-1,3-propanediol, and 3,4-dihydroxybenzaldehyde substantially inhibited melanogenesis with IC(50) values of 6.1-32 microM. With regard to the mechanism of action of silybins and isosilybins, the inhibition of tyrosinase activity suggested to be important. In addition, isosilybins A and B inhibited the mRNA expression of TRP-2, but silybins A and B oppositely enhanced the mRNA expression of tyrosinase and TRP-1 and -2 at 10 and/or 30 microM, and the inhibition of phosphorylation of extracellular signal-regulated kinases (ERK1/2) is involved in the enhanced expression of mRNA, at least in part, similar to that of PD98059.
|
Toxicity in mouse B16-4A5 cells assessed as inhibition of cell proliferation at 3 uM in presence of 1 mM theophylline after 72 hrs by WST8 dye reduction assay
|
Mus musculus
|
-4.9
%
|
|
Journal : Bioorg. Med. Chem.
Title : Melanogenesis inhibitors from the desert plant Anastatica hierochuntica in B16 melanoma cells.
Year : 2010
Volume : 18
Issue : 6
First Page : 2337
Last Page : 2345
Authors : Nakashima S, Matsuda H, Oda Y, Nakamura S, Xu F, Yoshikawa M.
Abstract : The methanolic extract from the whole plants of Anastatica hierochuntica, an Egyptian herbal medicine, was found to inhibit melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells. Among the constituents isolated, anastatin A, silybin A, isosilybins A and B, eriodictyol, luteolin, kaempferol, quercetin, hierochins A and B, (2R,3S)-2,3-dihydro-2-(3,4-dimethoxyphenyl)-3-hydroxymethyl-5-(2-formylvinyl)-7-hydroxybenzofuran, (+)-dehydrodiconiferyl alcohol, (+)-balanophonin, 1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-hydroxy-1-propenyl]-2-methoxyphenoxy}-1,3-propanediol, and 3,4-dihydroxybenzaldehyde substantially inhibited melanogenesis with IC(50) values of 6.1-32 microM. With regard to the mechanism of action of silybins and isosilybins, the inhibition of tyrosinase activity suggested to be important. In addition, isosilybins A and B inhibited the mRNA expression of TRP-2, but silybins A and B oppositely enhanced the mRNA expression of tyrosinase and TRP-1 and -2 at 10 and/or 30 microM, and the inhibition of phosphorylation of extracellular signal-regulated kinases (ERK1/2) is involved in the enhanced expression of mRNA, at least in part, similar to that of PD98059.
|
Toxicity in mouse B16-4A5 cells assessed as inhibition of cell proliferation at 10 uM in presence of 1 mM theophylline after 72 hrs by WST8 dye reduction assay
|
Mus musculus
|
4.0
%
|
|
Journal : Bioorg. Med. Chem.
Title : Melanogenesis inhibitors from the desert plant Anastatica hierochuntica in B16 melanoma cells.
Year : 2010
Volume : 18
Issue : 6
First Page : 2337
Last Page : 2345
Authors : Nakashima S, Matsuda H, Oda Y, Nakamura S, Xu F, Yoshikawa M.
Abstract : The methanolic extract from the whole plants of Anastatica hierochuntica, an Egyptian herbal medicine, was found to inhibit melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells. Among the constituents isolated, anastatin A, silybin A, isosilybins A and B, eriodictyol, luteolin, kaempferol, quercetin, hierochins A and B, (2R,3S)-2,3-dihydro-2-(3,4-dimethoxyphenyl)-3-hydroxymethyl-5-(2-formylvinyl)-7-hydroxybenzofuran, (+)-dehydrodiconiferyl alcohol, (+)-balanophonin, 1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-hydroxy-1-propenyl]-2-methoxyphenoxy}-1,3-propanediol, and 3,4-dihydroxybenzaldehyde substantially inhibited melanogenesis with IC(50) values of 6.1-32 microM. With regard to the mechanism of action of silybins and isosilybins, the inhibition of tyrosinase activity suggested to be important. In addition, isosilybins A and B inhibited the mRNA expression of TRP-2, but silybins A and B oppositely enhanced the mRNA expression of tyrosinase and TRP-1 and -2 at 10 and/or 30 microM, and the inhibition of phosphorylation of extracellular signal-regulated kinases (ERK1/2) is involved in the enhanced expression of mRNA, at least in part, similar to that of PD98059.
|
Toxicity in mouse B16-4A5 cells assessed as inhibition of cell proliferation at 30 uM in presence of 1 mM theophylline after 72 hrs by WST8 dye reduction assay
|
Mus musculus
|
23.4
%
|
|
Journal : Bioorg. Med. Chem.
Title : Melanogenesis inhibitors from the desert plant Anastatica hierochuntica in B16 melanoma cells.
Year : 2010
Volume : 18
Issue : 6
First Page : 2337
Last Page : 2345
Authors : Nakashima S, Matsuda H, Oda Y, Nakamura S, Xu F, Yoshikawa M.
Abstract : The methanolic extract from the whole plants of Anastatica hierochuntica, an Egyptian herbal medicine, was found to inhibit melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells. Among the constituents isolated, anastatin A, silybin A, isosilybins A and B, eriodictyol, luteolin, kaempferol, quercetin, hierochins A and B, (2R,3S)-2,3-dihydro-2-(3,4-dimethoxyphenyl)-3-hydroxymethyl-5-(2-formylvinyl)-7-hydroxybenzofuran, (+)-dehydrodiconiferyl alcohol, (+)-balanophonin, 1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-hydroxy-1-propenyl]-2-methoxyphenoxy}-1,3-propanediol, and 3,4-dihydroxybenzaldehyde substantially inhibited melanogenesis with IC(50) values of 6.1-32 microM. With regard to the mechanism of action of silybins and isosilybins, the inhibition of tyrosinase activity suggested to be important. In addition, isosilybins A and B inhibited the mRNA expression of TRP-2, but silybins A and B oppositely enhanced the mRNA expression of tyrosinase and TRP-1 and -2 at 10 and/or 30 microM, and the inhibition of phosphorylation of extracellular signal-regulated kinases (ERK1/2) is involved in the enhanced expression of mRNA, at least in part, similar to that of PD98059.
|
Inhibition of mushroom tyrosinase at 1 uM
|
Agaricus bisporus
|
6.4
%
|
|
Journal : Bioorg. Med. Chem.
Title : Melanogenesis inhibitors from the desert plant Anastatica hierochuntica in B16 melanoma cells.
Year : 2010
Volume : 18
Issue : 6
First Page : 2337
Last Page : 2345
Authors : Nakashima S, Matsuda H, Oda Y, Nakamura S, Xu F, Yoshikawa M.
Abstract : The methanolic extract from the whole plants of Anastatica hierochuntica, an Egyptian herbal medicine, was found to inhibit melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells. Among the constituents isolated, anastatin A, silybin A, isosilybins A and B, eriodictyol, luteolin, kaempferol, quercetin, hierochins A and B, (2R,3S)-2,3-dihydro-2-(3,4-dimethoxyphenyl)-3-hydroxymethyl-5-(2-formylvinyl)-7-hydroxybenzofuran, (+)-dehydrodiconiferyl alcohol, (+)-balanophonin, 1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-hydroxy-1-propenyl]-2-methoxyphenoxy}-1,3-propanediol, and 3,4-dihydroxybenzaldehyde substantially inhibited melanogenesis with IC(50) values of 6.1-32 microM. With regard to the mechanism of action of silybins and isosilybins, the inhibition of tyrosinase activity suggested to be important. In addition, isosilybins A and B inhibited the mRNA expression of TRP-2, but silybins A and B oppositely enhanced the mRNA expression of tyrosinase and TRP-1 and -2 at 10 and/or 30 microM, and the inhibition of phosphorylation of extracellular signal-regulated kinases (ERK1/2) is involved in the enhanced expression of mRNA, at least in part, similar to that of PD98059.
|
Inhibition of mushroom tyrosinase at 3 uM
|
Agaricus bisporus
|
7.1
%
|
|
Journal : Bioorg. Med. Chem.
Title : Melanogenesis inhibitors from the desert plant Anastatica hierochuntica in B16 melanoma cells.
Year : 2010
Volume : 18
Issue : 6
First Page : 2337
Last Page : 2345
Authors : Nakashima S, Matsuda H, Oda Y, Nakamura S, Xu F, Yoshikawa M.
Abstract : The methanolic extract from the whole plants of Anastatica hierochuntica, an Egyptian herbal medicine, was found to inhibit melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells. Among the constituents isolated, anastatin A, silybin A, isosilybins A and B, eriodictyol, luteolin, kaempferol, quercetin, hierochins A and B, (2R,3S)-2,3-dihydro-2-(3,4-dimethoxyphenyl)-3-hydroxymethyl-5-(2-formylvinyl)-7-hydroxybenzofuran, (+)-dehydrodiconiferyl alcohol, (+)-balanophonin, 1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-hydroxy-1-propenyl]-2-methoxyphenoxy}-1,3-propanediol, and 3,4-dihydroxybenzaldehyde substantially inhibited melanogenesis with IC(50) values of 6.1-32 microM. With regard to the mechanism of action of silybins and isosilybins, the inhibition of tyrosinase activity suggested to be important. In addition, isosilybins A and B inhibited the mRNA expression of TRP-2, but silybins A and B oppositely enhanced the mRNA expression of tyrosinase and TRP-1 and -2 at 10 and/or 30 microM, and the inhibition of phosphorylation of extracellular signal-regulated kinases (ERK1/2) is involved in the enhanced expression of mRNA, at least in part, similar to that of PD98059.
|
Inhibition of mushroom tyrosinase at 10 uM
|
Agaricus bisporus
|
9.2
%
|
|
Journal : Bioorg. Med. Chem.
Title : Melanogenesis inhibitors from the desert plant Anastatica hierochuntica in B16 melanoma cells.
Year : 2010
Volume : 18
Issue : 6
First Page : 2337
Last Page : 2345
Authors : Nakashima S, Matsuda H, Oda Y, Nakamura S, Xu F, Yoshikawa M.
Abstract : The methanolic extract from the whole plants of Anastatica hierochuntica, an Egyptian herbal medicine, was found to inhibit melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells. Among the constituents isolated, anastatin A, silybin A, isosilybins A and B, eriodictyol, luteolin, kaempferol, quercetin, hierochins A and B, (2R,3S)-2,3-dihydro-2-(3,4-dimethoxyphenyl)-3-hydroxymethyl-5-(2-formylvinyl)-7-hydroxybenzofuran, (+)-dehydrodiconiferyl alcohol, (+)-balanophonin, 1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-hydroxy-1-propenyl]-2-methoxyphenoxy}-1,3-propanediol, and 3,4-dihydroxybenzaldehyde substantially inhibited melanogenesis with IC(50) values of 6.1-32 microM. With regard to the mechanism of action of silybins and isosilybins, the inhibition of tyrosinase activity suggested to be important. In addition, isosilybins A and B inhibited the mRNA expression of TRP-2, but silybins A and B oppositely enhanced the mRNA expression of tyrosinase and TRP-1 and -2 at 10 and/or 30 microM, and the inhibition of phosphorylation of extracellular signal-regulated kinases (ERK1/2) is involved in the enhanced expression of mRNA, at least in part, similar to that of PD98059.
|
Inhibition of mushroom tyrosinase at 30 uM
|
Agaricus bisporus
|
12.1
%
|
|
Journal : Bioorg. Med. Chem.
Title : Melanogenesis inhibitors from the desert plant Anastatica hierochuntica in B16 melanoma cells.
Year : 2010
Volume : 18
Issue : 6
First Page : 2337
Last Page : 2345
Authors : Nakashima S, Matsuda H, Oda Y, Nakamura S, Xu F, Yoshikawa M.
Abstract : The methanolic extract from the whole plants of Anastatica hierochuntica, an Egyptian herbal medicine, was found to inhibit melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells. Among the constituents isolated, anastatin A, silybin A, isosilybins A and B, eriodictyol, luteolin, kaempferol, quercetin, hierochins A and B, (2R,3S)-2,3-dihydro-2-(3,4-dimethoxyphenyl)-3-hydroxymethyl-5-(2-formylvinyl)-7-hydroxybenzofuran, (+)-dehydrodiconiferyl alcohol, (+)-balanophonin, 1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-hydroxy-1-propenyl]-2-methoxyphenoxy}-1,3-propanediol, and 3,4-dihydroxybenzaldehyde substantially inhibited melanogenesis with IC(50) values of 6.1-32 microM. With regard to the mechanism of action of silybins and isosilybins, the inhibition of tyrosinase activity suggested to be important. In addition, isosilybins A and B inhibited the mRNA expression of TRP-2, but silybins A and B oppositely enhanced the mRNA expression of tyrosinase and TRP-1 and -2 at 10 and/or 30 microM, and the inhibition of phosphorylation of extracellular signal-regulated kinases (ERK1/2) is involved in the enhanced expression of mRNA, at least in part, similar to that of PD98059.
|
Inhibition of mushroom tyrosinase at 100 uM
|
Agaricus bisporus
|
17.6
%
|
|
Journal : Bioorg. Med. Chem.
Title : Melanogenesis inhibitors from the desert plant Anastatica hierochuntica in B16 melanoma cells.
Year : 2010
Volume : 18
Issue : 6
First Page : 2337
Last Page : 2345
Authors : Nakashima S, Matsuda H, Oda Y, Nakamura S, Xu F, Yoshikawa M.
Abstract : The methanolic extract from the whole plants of Anastatica hierochuntica, an Egyptian herbal medicine, was found to inhibit melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells. Among the constituents isolated, anastatin A, silybin A, isosilybins A and B, eriodictyol, luteolin, kaempferol, quercetin, hierochins A and B, (2R,3S)-2,3-dihydro-2-(3,4-dimethoxyphenyl)-3-hydroxymethyl-5-(2-formylvinyl)-7-hydroxybenzofuran, (+)-dehydrodiconiferyl alcohol, (+)-balanophonin, 1-(4-hydroxy-3-methoxyphenyl)-2-{4-[(E)-3-hydroxy-1-propenyl]-2-methoxyphenoxy}-1,3-propanediol, and 3,4-dihydroxybenzaldehyde substantially inhibited melanogenesis with IC(50) values of 6.1-32 microM. With regard to the mechanism of action of silybins and isosilybins, the inhibition of tyrosinase activity suggested to be important. In addition, isosilybins A and B inhibited the mRNA expression of TRP-2, but silybins A and B oppositely enhanced the mRNA expression of tyrosinase and TRP-1 and -2 at 10 and/or 30 microM, and the inhibition of phosphorylation of extracellular signal-regulated kinases (ERK1/2) is involved in the enhanced expression of mRNA, at least in part, similar to that of PD98059.
|
Inhibition of rat liver DNA topoisomerase 1 preincubated before addition of DNA
|
Rattus norvegicus
|
660.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Cytotoxicity and inhibition of DNA topoisomerase I of polyhydroxylated triterpenoids and triterpenoid glycosides.
Year : 2010
Volume : 20
Issue : 9
First Page : 2790
Last Page : 2796
Authors : Wang P, Ownby S, Zhang Z, Yuan W, Li S.
Abstract : Cytotoxicity and inhibition on human DNA topoisomerase I (TOP1) and II (TOP2) of 74 plant-originated triterpenoids and triterpenoid glycosides were investigated. The cytotoxic compounds are primarily polyhydroxylated oleananes (GI(50) of A549: 1.0-10.19 microM). Sixteen cytotoxic aesculiosides isolated from Aesculus pavia inhibited TOP1 catalytic activity by interacting directly with the free enzyme and preventing the formation of the DNA-TOP1 complex. Interestingly, hydrolysis of six active aesculiosides (1, 4, 6, 8, 10, and 23) lost their TOP1 activities but enhanced their cytotoxicities. None of the test compounds showed any activity against TOP2. Structure-activity relationship (SAR) investigations indicated that cytotoxic oleananes required at least one angeloyl moiety at either C-21 or C-22 but the sugar moiety at C-3 may decrease their cytotoxicities. An angeloyl or tigeloyl group at C-21 is required for oleananes to bind the free TOP1 enzyme although the type and length of acyl moiety at C-22 also affects their activity. However, sugar moiety at C-3 is necessary for their TOP1 activities.
|
Inhibition of Influenza A PR/8/34 H1N1 virus neuraminidase activity by MUN-ANA substrate based fluorimetric assay
|
Influenza A virus (A/Puerto Rico/8/1934(H1N1))
|
9.65
ug.mL-1
|
|
Journal : Eur. J. Med. Chem.
Title : QSAR study of flavonoids and biflavonoids as influenza H1N1 virus neuraminidase inhibitors.
Year : 2010
Volume : 45
Issue : 5
First Page : 1724
Last Page : 1730
Authors : Mercader AG, Pomilio AB.
Abstract : We performed a predictive analysis based on Quantitative Structure-Activity Relationships (QSAR) of a very important property of flavonoids which is the inhibition (IC50) of influenza H1N1 virus neuraminidase. The best linear model constructed from 20 molecular structures incorporated four molecular descriptors, selected from more than a thousand geometrical, topological, quantum-mechanical and electronic types of descriptors. The obtained model suggests that the activity depends on the electric charges, masses and polarizabilities of the atoms present in the molecule as well as its conformation. The model showed good predictive ability established by the theoretical and external test set validations.
|
Inhibition of human CYP1B1 by EROD assay
|
Homo sapiens
|
79.0
nM
|
|
Journal : Bioorg. Med. Chem.
Title : Selective inhibition of methoxyflavonoids on human CYP1B1 activity.
Year : 2010
Volume : 18
Issue : 17
First Page : 6310
Last Page : 6315
Authors : Takemura H, Itoh T, Yamamoto K, Sakakibara H, Shimoi K.
Abstract : Cytochrome P450 (CYP) 1B1 catalyzes 17beta-estradiol (E(2)) to predominantly carcinogenic 4-hydroxy-E(2), whereas CYP1A1 and 1A2 convert E(2) to non-carcinogenic 2-hydroxy-E(2). Hence, selective inhibition of CYP1B1 is recognized to be beneficial for the prevention of E(2) related breast cancer. In this study, we first evaluated the structure-property relationship of 18 major flavonoids on inhibiting enzymatic activity of CYP1A1, 1A2 and 1B1 by using an ethoxyresorufin O-deethylation assay. Flavones and flavonols indicated relatively strong inhibitory effects on CYP1s compared with flavanone that does not have the double bond between C-positions 2 and 3 on the C-ring. Flavonoids used in this study selectively inhibited CYP1B1 activity. In particular, methoxy types of flavones and flavonols such as chrysoeriol and isorhamnetin showed strong and selective inhibition against CYP1B1. To understand why selective inhibition was observed, we carried out a molecular docking analysis of these methoxyflavonoids with the 2-3 double bond and CYP1s. The results suggested that chrysoeriol and isorhamnetin fit well into the active site of CYP1B1, but do not fit into the active site of CYP1A2 and 1A1 because of steric collisions between the methoxy substituent of these methoxyflavonoids and Ser-122 in CYP1A1 and Thr-124 in CYP1A2. In conclusion, our results demonstrate: (1) strong inhibitory effects of flavonoids on CYP1 activities require the 2-3 double bond on the C-ring; (2) methoxyflavonoids with the 2-3 double bond had strong and selective inhibition against CYP1B1, suggesting chemopreventive flavonoids for E(2) related breast cancer; and (3) binding specificity of these methoxyflavonoids is based on the interactions between the methoxy groups and specific CYP1s residues.
|
Inhibition of NOX4 expressed in HEK293 FS cells at 10 uM assessed as H2O2 production by H2O2/Tyr/LPO assay
|
None
|
106.0
%
|
|
Journal : J. Med. Chem.
Title : Small-molecule inhibitors of NADPH oxidase 4.
Year : 2010
Volume : 53
Issue : 18
First Page : 6758
Last Page : 6762
Authors : Borbély G, Szabadkai I, Horváth Z, Markó P, Varga Z, Breza N, Baska F, Vántus T, Huszár M, Geiszt M, Hunyady L, Buday L, Orfi L, Kéri G.
Abstract : NOX enzymes are the major contributors in many oxidative damage related diseases. Unfortunately, at present no specific NOX inhibitor is available. Here, we describe the discovery and development of novel NOX4 inhibitors. Compound libraries were tested in a cell-based assay as a primary screen, monitoring H2O2 production. Twenty-four compounds inhibited Nox4 activity with low-micromolar IC(50) values of which three were selected for further drug development.
|
Inhibition of NOX4 expressed in HEK293 FS cells assessed as H2O2 production by H2O2/Tyr/LPO assay
|
None
|
850.0
nM
|
|
Journal : J. Med. Chem.
Title : Small-molecule inhibitors of NADPH oxidase 4.
Year : 2010
Volume : 53
Issue : 18
First Page : 6758
Last Page : 6762
Authors : Borbély G, Szabadkai I, Horváth Z, Markó P, Varga Z, Breza N, Baska F, Vántus T, Huszár M, Geiszt M, Hunyady L, Buday L, Orfi L, Kéri G.
Abstract : NOX enzymes are the major contributors in many oxidative damage related diseases. Unfortunately, at present no specific NOX inhibitor is available. Here, we describe the discovery and development of novel NOX4 inhibitors. Compound libraries were tested in a cell-based assay as a primary screen, monitoring H2O2 production. Twenty-four compounds inhibited Nox4 activity with low-micromolar IC(50) values of which three were selected for further drug development.
|
Cytotoxicity against human free style HEK293 cells after 72 hrs
|
Homo sapiens
|
-4.47
%
|
|
Journal : J. Med. Chem.
Title : Small-molecule inhibitors of NADPH oxidase 4.
Year : 2010
Volume : 53
Issue : 18
First Page : 6758
Last Page : 6762
Authors : Borbély G, Szabadkai I, Horváth Z, Markó P, Varga Z, Breza N, Baska F, Vántus T, Huszár M, Geiszt M, Hunyady L, Buday L, Orfi L, Kéri G.
Abstract : NOX enzymes are the major contributors in many oxidative damage related diseases. Unfortunately, at present no specific NOX inhibitor is available. Here, we describe the discovery and development of novel NOX4 inhibitors. Compound libraries were tested in a cell-based assay as a primary screen, monitoring H2O2 production. Twenty-four compounds inhibited Nox4 activity with low-micromolar IC(50) values of which three were selected for further drug development.
|
Inhibition of NOX4 expressed in HEK293 FS cells at 10 uM assessed as H2O2 production by H2O2/Tyr/LPO assay substituted with 3 uM H2O2
|
None
|
110.36
%
|
|
Journal : J. Med. Chem.
Title : Small-molecule inhibitors of NADPH oxidase 4.
Year : 2010
Volume : 53
Issue : 18
First Page : 6758
Last Page : 6762
Authors : Borbély G, Szabadkai I, Horváth Z, Markó P, Varga Z, Breza N, Baska F, Vántus T, Huszár M, Geiszt M, Hunyady L, Buday L, Orfi L, Kéri G.
Abstract : NOX enzymes are the major contributors in many oxidative damage related diseases. Unfortunately, at present no specific NOX inhibitor is available. Here, we describe the discovery and development of novel NOX4 inhibitors. Compound libraries were tested in a cell-based assay as a primary screen, monitoring H2O2 production. Twenty-four compounds inhibited Nox4 activity with low-micromolar IC(50) values of which three were selected for further drug development.
|
Cytotoxicity against human HepG2 cells by MTT assay
|
Homo sapiens
|
7.36
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Ixorapeptide I and ixorapeptide II, bioactive peptides isolated from Ixora coccinea.
Year : 2010
Volume : 20
Issue : 24
First Page : 7354
Last Page : 7357
Authors : Lee CL, Liao YC, Hwang TL, Wu CC, Chang FR, Wu YC.
Abstract : Two novel derivatized peptides, designated as ixorapeptide I (1) and ixorapeptide II (2), in addition to 28 other known compounds, were isolated from the MeOH extract of Ixora coccinea using bioassay-guided fractionation. The structures of metabolites 1 and 2 were determined by interpretation of the spectroscopic data and Marfey's method. Compound 1 exhibited selective potency against Hep3B liver cancer cell line with an IC(50) value of 3.36 μg/mL, and compound 2 did not show notable cytotoxicity toward cancer cell lines but could inhibit superoxide anion generation and elastase release with IC(50) values of 0.21 and 0.27 μg/mL, respectively. Moreover, kaempferol and luteolin from this plant showed inhibition with IC(50) values of 3.55 and 2.56 μg/mL, respectively on platelet aggregation induced by collagen.
|
Cytotoxicity against human Hep3B cells by MTT assay
|
Homo sapiens
|
8.03
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Ixorapeptide I and ixorapeptide II, bioactive peptides isolated from Ixora coccinea.
Year : 2010
Volume : 20
Issue : 24
First Page : 7354
Last Page : 7357
Authors : Lee CL, Liao YC, Hwang TL, Wu CC, Chang FR, Wu YC.
Abstract : Two novel derivatized peptides, designated as ixorapeptide I (1) and ixorapeptide II (2), in addition to 28 other known compounds, were isolated from the MeOH extract of Ixora coccinea using bioassay-guided fractionation. The structures of metabolites 1 and 2 were determined by interpretation of the spectroscopic data and Marfey's method. Compound 1 exhibited selective potency against Hep3B liver cancer cell line with an IC(50) value of 3.36 μg/mL, and compound 2 did not show notable cytotoxicity toward cancer cell lines but could inhibit superoxide anion generation and elastase release with IC(50) values of 0.21 and 0.27 μg/mL, respectively. Moreover, kaempferol and luteolin from this plant showed inhibition with IC(50) values of 3.55 and 2.56 μg/mL, respectively on platelet aggregation induced by collagen.
|
Cytotoxicity against human Ca9-22 cells by MTT assay
|
Homo sapiens
|
8.55
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Ixorapeptide I and ixorapeptide II, bioactive peptides isolated from Ixora coccinea.
Year : 2010
Volume : 20
Issue : 24
First Page : 7354
Last Page : 7357
Authors : Lee CL, Liao YC, Hwang TL, Wu CC, Chang FR, Wu YC.
Abstract : Two novel derivatized peptides, designated as ixorapeptide I (1) and ixorapeptide II (2), in addition to 28 other known compounds, were isolated from the MeOH extract of Ixora coccinea using bioassay-guided fractionation. The structures of metabolites 1 and 2 were determined by interpretation of the spectroscopic data and Marfey's method. Compound 1 exhibited selective potency against Hep3B liver cancer cell line with an IC(50) value of 3.36 μg/mL, and compound 2 did not show notable cytotoxicity toward cancer cell lines but could inhibit superoxide anion generation and elastase release with IC(50) values of 0.21 and 0.27 μg/mL, respectively. Moreover, kaempferol and luteolin from this plant showed inhibition with IC(50) values of 3.55 and 2.56 μg/mL, respectively on platelet aggregation induced by collagen.
|
Cytotoxicity against human A549 cells by MTT assay
|
Homo sapiens
|
10.23
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Ixorapeptide I and ixorapeptide II, bioactive peptides isolated from Ixora coccinea.
Year : 2010
Volume : 20
Issue : 24
First Page : 7354
Last Page : 7357
Authors : Lee CL, Liao YC, Hwang TL, Wu CC, Chang FR, Wu YC.
Abstract : Two novel derivatized peptides, designated as ixorapeptide I (1) and ixorapeptide II (2), in addition to 28 other known compounds, were isolated from the MeOH extract of Ixora coccinea using bioassay-guided fractionation. The structures of metabolites 1 and 2 were determined by interpretation of the spectroscopic data and Marfey's method. Compound 1 exhibited selective potency against Hep3B liver cancer cell line with an IC(50) value of 3.36 μg/mL, and compound 2 did not show notable cytotoxicity toward cancer cell lines but could inhibit superoxide anion generation and elastase release with IC(50) values of 0.21 and 0.27 μg/mL, respectively. Moreover, kaempferol and luteolin from this plant showed inhibition with IC(50) values of 3.55 and 2.56 μg/mL, respectively on platelet aggregation induced by collagen.
|
Cytotoxicity against human MCF7 cells by MTT assay
|
Homo sapiens
|
9.5
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Ixorapeptide I and ixorapeptide II, bioactive peptides isolated from Ixora coccinea.
Year : 2010
Volume : 20
Issue : 24
First Page : 7354
Last Page : 7357
Authors : Lee CL, Liao YC, Hwang TL, Wu CC, Chang FR, Wu YC.
Abstract : Two novel derivatized peptides, designated as ixorapeptide I (1) and ixorapeptide II (2), in addition to 28 other known compounds, were isolated from the MeOH extract of Ixora coccinea using bioassay-guided fractionation. The structures of metabolites 1 and 2 were determined by interpretation of the spectroscopic data and Marfey's method. Compound 1 exhibited selective potency against Hep3B liver cancer cell line with an IC(50) value of 3.36 μg/mL, and compound 2 did not show notable cytotoxicity toward cancer cell lines but could inhibit superoxide anion generation and elastase release with IC(50) values of 0.21 and 0.27 μg/mL, respectively. Moreover, kaempferol and luteolin from this plant showed inhibition with IC(50) values of 3.55 and 2.56 μg/mL, respectively on platelet aggregation induced by collagen.
|
Cytotoxicity against human MDA-MB-231 cells by MTT assay
|
Homo sapiens
|
9.65
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Ixorapeptide I and ixorapeptide II, bioactive peptides isolated from Ixora coccinea.
Year : 2010
Volume : 20
Issue : 24
First Page : 7354
Last Page : 7357
Authors : Lee CL, Liao YC, Hwang TL, Wu CC, Chang FR, Wu YC.
Abstract : Two novel derivatized peptides, designated as ixorapeptide I (1) and ixorapeptide II (2), in addition to 28 other known compounds, were isolated from the MeOH extract of Ixora coccinea using bioassay-guided fractionation. The structures of metabolites 1 and 2 were determined by interpretation of the spectroscopic data and Marfey's method. Compound 1 exhibited selective potency against Hep3B liver cancer cell line with an IC(50) value of 3.36 μg/mL, and compound 2 did not show notable cytotoxicity toward cancer cell lines but could inhibit superoxide anion generation and elastase release with IC(50) values of 0.21 and 0.27 μg/mL, respectively. Moreover, kaempferol and luteolin from this plant showed inhibition with IC(50) values of 3.55 and 2.56 μg/mL, respectively on platelet aggregation induced by collagen.
|
Antiaggregatory activity in human platelets assessed as inhibition of collagen-induced platelet aggregation by aggregometry
|
Homo sapiens
|
2.56
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Ixorapeptide I and ixorapeptide II, bioactive peptides isolated from Ixora coccinea.
Year : 2010
Volume : 20
Issue : 24
First Page : 7354
Last Page : 7357
Authors : Lee CL, Liao YC, Hwang TL, Wu CC, Chang FR, Wu YC.
Abstract : Two novel derivatized peptides, designated as ixorapeptide I (1) and ixorapeptide II (2), in addition to 28 other known compounds, were isolated from the MeOH extract of Ixora coccinea using bioassay-guided fractionation. The structures of metabolites 1 and 2 were determined by interpretation of the spectroscopic data and Marfey's method. Compound 1 exhibited selective potency against Hep3B liver cancer cell line with an IC(50) value of 3.36 μg/mL, and compound 2 did not show notable cytotoxicity toward cancer cell lines but could inhibit superoxide anion generation and elastase release with IC(50) values of 0.21 and 0.27 μg/mL, respectively. Moreover, kaempferol and luteolin from this plant showed inhibition with IC(50) values of 3.55 and 2.56 μg/mL, respectively on platelet aggregation induced by collagen.
|
Antiaggregatory activity in human platelets assessed as inhibition of thrombin-induced platelet aggregation by aggregometry
|
Homo sapiens
|
50.0
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Ixorapeptide I and ixorapeptide II, bioactive peptides isolated from Ixora coccinea.
Year : 2010
Volume : 20
Issue : 24
First Page : 7354
Last Page : 7357
Authors : Lee CL, Liao YC, Hwang TL, Wu CC, Chang FR, Wu YC.
Abstract : Two novel derivatized peptides, designated as ixorapeptide I (1) and ixorapeptide II (2), in addition to 28 other known compounds, were isolated from the MeOH extract of Ixora coccinea using bioassay-guided fractionation. The structures of metabolites 1 and 2 were determined by interpretation of the spectroscopic data and Marfey's method. Compound 1 exhibited selective potency against Hep3B liver cancer cell line with an IC(50) value of 3.36 μg/mL, and compound 2 did not show notable cytotoxicity toward cancer cell lines but could inhibit superoxide anion generation and elastase release with IC(50) values of 0.21 and 0.27 μg/mL, respectively. Moreover, kaempferol and luteolin from this plant showed inhibition with IC(50) values of 3.55 and 2.56 μg/mL, respectively on platelet aggregation induced by collagen.
|
Inhibition of CYP1A1 EROD activity assessed as inhibition of deethylation of 7-ethoxyresorufin to resorufin
|
None
|
890.0
nM
|
|
Journal : Bioorg. Med. Chem.
Title : Comparative CYP1A1 and CYP1B1 substrate and inhibitor profile of dietary flavonoids.
Year : 2011
Volume : 19
Issue : 9
First Page : 2842
Last Page : 2849
Authors : Androutsopoulos VP, Papakyriakou A, Vourloumis D, Spandidos DA.
Abstract : CYP1A1 and CYP1B1 are two extrahepatic enzymes that have been implicated in carcinogenesis and cancer progression. Selective inhibition of CYP1A1 and CYP1B1 by dietary constituents, notably the class of flavonoids, is a widely accepted paradigm that supports the concept of dietary chemoprevention. In parallel, recent studies have documented the ability of CYP1 enzymes to selectively metabolize dietary flavonoids to conversion products that inhibit cancer cell proliferation. In the present study we have examined the inhibition of CYP1A1 and CYP1B1-catalyzed EROD activity by 14 different flavonoids containing methoxy- and hydroxyl-group substitutions as well as the metabolism of the monomethoxylated CYP1-flavonoid inhibitor acacetin and the poly-methoxylated flavone eupatorin-5-methyl ether by recombinant CYP1A1 and CYP1B1. The most potent inhibitors of CYP1-EROD activity were the methoxylated flavones acacetin, diosmetin, eupatorin and the di-hydroxylated flavone chrysin, indicating that the 4'-OCH(3) group at the B ring and the 5,7-dihydroxy motif at the A ring play a prominent role in EROD inhibition. Potent inhibition of CYP1B1 EROD activity was also obtained for the poly-hydroxylated flavonols quercetin and myricetin. HPLC metabolism of acacetin by CYP1A1 and CYP1B1 revealed the formation of the structurally similar flavone apigenin by demethylation at the 4'-position of the B ring, whereas the flavone eupatorin-5-methyl ether was metabolized to an as yet unidentified metabolite assigned E(5)M1. Eupatorin-5-methyl ether demonstrated a submicromolar IC(50) in the CYP1-expressing cancer cell line MDA-MB 468, while it was considerably inactive in the normal cell line MCF-10A. Homology modeling in conjunction with molecular docking calculations were employed in an effort to rationalize the activity of these flavonoids based on their CYP1-binding mode. Taken together the data suggest that dietary flavonoids exhibit three distinct modes of action with regard to cancer prevention, based on their hydroxyl and methoxy decoration: (1) inhibitors of CYP1 enzymatic activity, (2) CYP1 substrates and (3) substrates and inhibitors of CYP1 enzymes.
|
Inhibition of CYP1B1 EROD activity assessed as inhibition of deethylation of 7-ethoxyresorufin to resorufin
|
None
|
56.0
nM
|
|
Journal : Bioorg. Med. Chem.
Title : Comparative CYP1A1 and CYP1B1 substrate and inhibitor profile of dietary flavonoids.
Year : 2011
Volume : 19
Issue : 9
First Page : 2842
Last Page : 2849
Authors : Androutsopoulos VP, Papakyriakou A, Vourloumis D, Spandidos DA.
Abstract : CYP1A1 and CYP1B1 are two extrahepatic enzymes that have been implicated in carcinogenesis and cancer progression. Selective inhibition of CYP1A1 and CYP1B1 by dietary constituents, notably the class of flavonoids, is a widely accepted paradigm that supports the concept of dietary chemoprevention. In parallel, recent studies have documented the ability of CYP1 enzymes to selectively metabolize dietary flavonoids to conversion products that inhibit cancer cell proliferation. In the present study we have examined the inhibition of CYP1A1 and CYP1B1-catalyzed EROD activity by 14 different flavonoids containing methoxy- and hydroxyl-group substitutions as well as the metabolism of the monomethoxylated CYP1-flavonoid inhibitor acacetin and the poly-methoxylated flavone eupatorin-5-methyl ether by recombinant CYP1A1 and CYP1B1. The most potent inhibitors of CYP1-EROD activity were the methoxylated flavones acacetin, diosmetin, eupatorin and the di-hydroxylated flavone chrysin, indicating that the 4'-OCH(3) group at the B ring and the 5,7-dihydroxy motif at the A ring play a prominent role in EROD inhibition. Potent inhibition of CYP1B1 EROD activity was also obtained for the poly-hydroxylated flavonols quercetin and myricetin. HPLC metabolism of acacetin by CYP1A1 and CYP1B1 revealed the formation of the structurally similar flavone apigenin by demethylation at the 4'-position of the B ring, whereas the flavone eupatorin-5-methyl ether was metabolized to an as yet unidentified metabolite assigned E(5)M1. Eupatorin-5-methyl ether demonstrated a submicromolar IC(50) in the CYP1-expressing cancer cell line MDA-MB 468, while it was considerably inactive in the normal cell line MCF-10A. Homology modeling in conjunction with molecular docking calculations were employed in an effort to rationalize the activity of these flavonoids based on their CYP1-binding mode. Taken together the data suggest that dietary flavonoids exhibit three distinct modes of action with regard to cancer prevention, based on their hydroxyl and methoxy decoration: (1) inhibitors of CYP1 enzymatic activity, (2) CYP1 substrates and (3) substrates and inhibitors of CYP1 enzymes.
|
Inhibition of Xanthomonas oryzae pv. oryzae KS-1-21 uridyltransferase domain of GlmU activity by ion-pair reverse-phase HPLC analysis
|
Xanthomonas oryzae pv. oryzae
|
810.0
nM
|
|
Journal : Eur. J. Med. Chem.
Title : Structure-based virtual screening of novel inhibitors of the uridyltransferase activity of Xanthomonas oryzae pv. oryzae GlmU.
Year : 2012
Volume : 53
First Page : 150
Last Page : 158
Authors : Min J, Lin D, Zhang Q, Zhang J, Yu Z.
Abstract : N-Acetylglucosamine-1-phosphate uridyltransferase (GlmU) catalyzes the formation of UDP-GlcNAc, a fundamental precursor in cell wall biosynthesis. GlmU represents an attractive target for new antibacterial agents. In this study, a theoretical three-dimensional (3D) structure of GlmU from Xanthomonas oryzae pv. oryzae (Xo-GlmU) was generated, and the ligand-receptor interaction was investigated by molecular docking. Then a structure-based virtual screening was performed, three hit compounds were identified as specific inhibitors of the uridyltransferase activity of Xo-GlmU, with IC(50) values in the 0.81-23.21 μM range. Subsequently, the mode-of-inhibition and K(i) values of the three inhibitors were confirmed. The minimum inhibitory concentrations (MICs) of the candidate compounds for X. oryzae pv. oryzae (Xoo) were also determined. The research provided novel chemical scaffolds for antimicrobial drug discovery.
|
Competitive inhibition of Xanthomonas oryzae pv. Oryzae KS-1-21 GlmU using 0.25 to 0.05 mM GlcNAc-1-p and 500 uM UTP by Lineweaver-Burk plot analysis
|
Xanthomonas oryzae pv. oryzae
|
440.0
nM
|
|
Journal : Eur. J. Med. Chem.
Title : Structure-based virtual screening of novel inhibitors of the uridyltransferase activity of Xanthomonas oryzae pv. oryzae GlmU.
Year : 2012
Volume : 53
First Page : 150
Last Page : 158
Authors : Min J, Lin D, Zhang Q, Zhang J, Yu Z.
Abstract : N-Acetylglucosamine-1-phosphate uridyltransferase (GlmU) catalyzes the formation of UDP-GlcNAc, a fundamental precursor in cell wall biosynthesis. GlmU represents an attractive target for new antibacterial agents. In this study, a theoretical three-dimensional (3D) structure of GlmU from Xanthomonas oryzae pv. oryzae (Xo-GlmU) was generated, and the ligand-receptor interaction was investigated by molecular docking. Then a structure-based virtual screening was performed, three hit compounds were identified as specific inhibitors of the uridyltransferase activity of Xo-GlmU, with IC(50) values in the 0.81-23.21 μM range. Subsequently, the mode-of-inhibition and K(i) values of the three inhibitors were confirmed. The minimum inhibitory concentrations (MICs) of the candidate compounds for X. oryzae pv. oryzae (Xoo) were also determined. The research provided novel chemical scaffolds for antimicrobial drug discovery.
|
Uncompetitive inhibition of Xanthomonas oryzae pv. Oryzae KS-1-21 GlmU using varying concentration of UTP and 500 uM GlcNAc-1-p by Lineweaver-Burk plot analysis
|
Xanthomonas oryzae pv. oryzae
|
990.0
nM
|
|
Journal : Eur. J. Med. Chem.
Title : Structure-based virtual screening of novel inhibitors of the uridyltransferase activity of Xanthomonas oryzae pv. oryzae GlmU.
Year : 2012
Volume : 53
First Page : 150
Last Page : 158
Authors : Min J, Lin D, Zhang Q, Zhang J, Yu Z.
Abstract : N-Acetylglucosamine-1-phosphate uridyltransferase (GlmU) catalyzes the formation of UDP-GlcNAc, a fundamental precursor in cell wall biosynthesis. GlmU represents an attractive target for new antibacterial agents. In this study, a theoretical three-dimensional (3D) structure of GlmU from Xanthomonas oryzae pv. oryzae (Xo-GlmU) was generated, and the ligand-receptor interaction was investigated by molecular docking. Then a structure-based virtual screening was performed, three hit compounds were identified as specific inhibitors of the uridyltransferase activity of Xo-GlmU, with IC(50) values in the 0.81-23.21 μM range. Subsequently, the mode-of-inhibition and K(i) values of the three inhibitors were confirmed. The minimum inhibitory concentrations (MICs) of the candidate compounds for X. oryzae pv. oryzae (Xoo) were also determined. The research provided novel chemical scaffolds for antimicrobial drug discovery.
|
Inhibition of human recombinant MMP12 catalytic domain incubated for 20 mins by fluorimetric assay
|
Homo sapiens
|
980.0
nM
|
|
Journal : Bioorg. Med. Chem.
Title : Natural products as a gold mine for selective matrix metalloproteinases inhibitors.
Year : 2012
Volume : 20
Issue : 13
First Page : 4164
Last Page : 4171
Authors : Wang L, Li X, Zhang S, Lu W, Liao S, Liu X, Shan L, Shen X, Jiang H, Zhang W, Huang J, Li H.
Abstract : Nineteen natural compounds with diverse structures are identified as potential MMPIs using structure-based virtual screening from 4000 natural products. Hydroxycinnamic acid or analogs of natural products are important for potent inhibitory and selectivity against MMPs, and the solvent effect in the S1' pocket can affect the hydrophobic interactions and hydrogen bonds between MMPIs and MMPS, making MMPIs exhibit certain selectivity for a specific MMP isoenzyme. Furthermore, compound 5 can reduce the expression of both MMP-2 and active-MMP-9, and suppress the migration of MDA-MB-231 tumor cell in a wound healing assay, which may be further developed as an anticancer agent.
|
Inhibition of human recombinant MMP2 catalytic domain at 10 uM incubated for 20 mins by fluorimetric assay
|
Homo sapiens
|
30.0
%
|
|
Journal : Bioorg. Med. Chem.
Title : Natural products as a gold mine for selective matrix metalloproteinases inhibitors.
Year : 2012
Volume : 20
Issue : 13
First Page : 4164
Last Page : 4171
Authors : Wang L, Li X, Zhang S, Lu W, Liao S, Liu X, Shan L, Shen X, Jiang H, Zhang W, Huang J, Li H.
Abstract : Nineteen natural compounds with diverse structures are identified as potential MMPIs using structure-based virtual screening from 4000 natural products. Hydroxycinnamic acid or analogs of natural products are important for potent inhibitory and selectivity against MMPs, and the solvent effect in the S1' pocket can affect the hydrophobic interactions and hydrogen bonds between MMPIs and MMPS, making MMPIs exhibit certain selectivity for a specific MMP isoenzyme. Furthermore, compound 5 can reduce the expression of both MMP-2 and active-MMP-9, and suppress the migration of MDA-MB-231 tumor cell in a wound healing assay, which may be further developed as an anticancer agent.
|
Inhibition of human recombinant MMP3 catalytic domain at 10 uM incubated for 20 mins by fluorimetric assay
|
Homo sapiens
|
30.0
%
|
|
Journal : Bioorg. Med. Chem.
Title : Natural products as a gold mine for selective matrix metalloproteinases inhibitors.
Year : 2012
Volume : 20
Issue : 13
First Page : 4164
Last Page : 4171
Authors : Wang L, Li X, Zhang S, Lu W, Liao S, Liu X, Shan L, Shen X, Jiang H, Zhang W, Huang J, Li H.
Abstract : Nineteen natural compounds with diverse structures are identified as potential MMPIs using structure-based virtual screening from 4000 natural products. Hydroxycinnamic acid or analogs of natural products are important for potent inhibitory and selectivity against MMPs, and the solvent effect in the S1' pocket can affect the hydrophobic interactions and hydrogen bonds between MMPIs and MMPS, making MMPIs exhibit certain selectivity for a specific MMP isoenzyme. Furthermore, compound 5 can reduce the expression of both MMP-2 and active-MMP-9, and suppress the migration of MDA-MB-231 tumor cell in a wound healing assay, which may be further developed as an anticancer agent.
|
Inhibition of human recombinant MMP9 catalytic domain at 10 uM incubated for 20 mins by fluorimetric assay
|
Homo sapiens
|
30.0
%
|
|
Journal : Bioorg. Med. Chem.
Title : Natural products as a gold mine for selective matrix metalloproteinases inhibitors.
Year : 2012
Volume : 20
Issue : 13
First Page : 4164
Last Page : 4171
Authors : Wang L, Li X, Zhang S, Lu W, Liao S, Liu X, Shan L, Shen X, Jiang H, Zhang W, Huang J, Li H.
Abstract : Nineteen natural compounds with diverse structures are identified as potential MMPIs using structure-based virtual screening from 4000 natural products. Hydroxycinnamic acid or analogs of natural products are important for potent inhibitory and selectivity against MMPs, and the solvent effect in the S1' pocket can affect the hydrophobic interactions and hydrogen bonds between MMPIs and MMPS, making MMPIs exhibit certain selectivity for a specific MMP isoenzyme. Furthermore, compound 5 can reduce the expression of both MMP-2 and active-MMP-9, and suppress the migration of MDA-MB-231 tumor cell in a wound healing assay, which may be further developed as an anticancer agent.
|
Inhibition of human recombinant MMP12 catalytic domain at 10 uM incubated for 20 mins by fluorimetric assay
|
Homo sapiens
|
30.0
%
|
|
Journal : Bioorg. Med. Chem.
Title : Natural products as a gold mine for selective matrix metalloproteinases inhibitors.
Year : 2012
Volume : 20
Issue : 13
First Page : 4164
Last Page : 4171
Authors : Wang L, Li X, Zhang S, Lu W, Liao S, Liu X, Shan L, Shen X, Jiang H, Zhang W, Huang J, Li H.
Abstract : Nineteen natural compounds with diverse structures are identified as potential MMPIs using structure-based virtual screening from 4000 natural products. Hydroxycinnamic acid or analogs of natural products are important for potent inhibitory and selectivity against MMPs, and the solvent effect in the S1' pocket can affect the hydrophobic interactions and hydrogen bonds between MMPIs and MMPS, making MMPIs exhibit certain selectivity for a specific MMP isoenzyme. Furthermore, compound 5 can reduce the expression of both MMP-2 and active-MMP-9, and suppress the migration of MDA-MB-231 tumor cell in a wound healing assay, which may be further developed as an anticancer agent.
|
Inhibition of human recombinant MMP13 catalytic domain at 10 uM incubated for 20 mins by fluorimetric assay
|
Homo sapiens
|
30.0
%
|
|
Journal : Bioorg. Med. Chem.
Title : Natural products as a gold mine for selective matrix metalloproteinases inhibitors.
Year : 2012
Volume : 20
Issue : 13
First Page : 4164
Last Page : 4171
Authors : Wang L, Li X, Zhang S, Lu W, Liao S, Liu X, Shan L, Shen X, Jiang H, Zhang W, Huang J, Li H.
Abstract : Nineteen natural compounds with diverse structures are identified as potential MMPIs using structure-based virtual screening from 4000 natural products. Hydroxycinnamic acid or analogs of natural products are important for potent inhibitory and selectivity against MMPs, and the solvent effect in the S1' pocket can affect the hydrophobic interactions and hydrogen bonds between MMPIs and MMPS, making MMPIs exhibit certain selectivity for a specific MMP isoenzyme. Furthermore, compound 5 can reduce the expression of both MMP-2 and active-MMP-9, and suppress the migration of MDA-MB-231 tumor cell in a wound healing assay, which may be further developed as an anticancer agent.
|
Antioxidant activity assessed as DPPH free radical scavenging activity
|
None
|
44.18
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis, biological evaluation of 5-carbomethoxymethyl-7-hydroxy-2-pentylchromone, 5-carboethoxymethyl-4',7-dihydroxyflavone and their analogues.
Year : 2012
Volume : 22
Issue : 14
First Page : 4891
Last Page : 4895
Authors : Kamal A, Murty JN, Viswanath A, Sujitha P, Ganesh Kumar C.
Abstract : In this letter, we describe the first synthesis of two recently isolated flavones 5-carbomethoxymethyl-7-hydroxy-2-pentylchromone (3a), 5-carboethoxymethyl-4',7-dihydroxyflavone (3b) and their derivatives (3c-t), evaluated for their antimicrobial, antioxidant and anticancer activities. Most of the synthesized compounds exhibited antimicrobial activity against the tested microbial strains and some of these compounds were found to be more potent as compared to the standard drugs like neomycin and luteolin. Interestingly, some of these synthesized compounds also showed moderate antioxidant property.
|
Antioxidant activity assessed as superoxide radical scavenging activity
|
None
|
31.01
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis, biological evaluation of 5-carbomethoxymethyl-7-hydroxy-2-pentylchromone, 5-carboethoxymethyl-4',7-dihydroxyflavone and their analogues.
Year : 2012
Volume : 22
Issue : 14
First Page : 4891
Last Page : 4895
Authors : Kamal A, Murty JN, Viswanath A, Sujitha P, Ganesh Kumar C.
Abstract : In this letter, we describe the first synthesis of two recently isolated flavones 5-carbomethoxymethyl-7-hydroxy-2-pentylchromone (3a), 5-carboethoxymethyl-4',7-dihydroxyflavone (3b) and their derivatives (3c-t), evaluated for their antimicrobial, antioxidant and anticancer activities. Most of the synthesized compounds exhibited antimicrobial activity against the tested microbial strains and some of these compounds were found to be more potent as compared to the standard drugs like neomycin and luteolin. Interestingly, some of these synthesized compounds also showed moderate antioxidant property.
|
Antioxidant activity of the compound assessed as inhibition of lipid peroxidation
|
None
|
134.1
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis, biological evaluation of 5-carbomethoxymethyl-7-hydroxy-2-pentylchromone, 5-carboethoxymethyl-4',7-dihydroxyflavone and their analogues.
Year : 2012
Volume : 22
Issue : 14
First Page : 4891
Last Page : 4895
Authors : Kamal A, Murty JN, Viswanath A, Sujitha P, Ganesh Kumar C.
Abstract : In this letter, we describe the first synthesis of two recently isolated flavones 5-carbomethoxymethyl-7-hydroxy-2-pentylchromone (3a), 5-carboethoxymethyl-4',7-dihydroxyflavone (3b) and their derivatives (3c-t), evaluated for their antimicrobial, antioxidant and anticancer activities. Most of the synthesized compounds exhibited antimicrobial activity against the tested microbial strains and some of these compounds were found to be more potent as compared to the standard drugs like neomycin and luteolin. Interestingly, some of these synthesized compounds also showed moderate antioxidant property.
|
Antioxidant activity in erythrocytes assessed as inhibition of hemolysis
|
None
|
122.0
ug.mL-1
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis, biological evaluation of 5-carbomethoxymethyl-7-hydroxy-2-pentylchromone, 5-carboethoxymethyl-4',7-dihydroxyflavone and their analogues.
Year : 2012
Volume : 22
Issue : 14
First Page : 4891
Last Page : 4895
Authors : Kamal A, Murty JN, Viswanath A, Sujitha P, Ganesh Kumar C.
Abstract : In this letter, we describe the first synthesis of two recently isolated flavones 5-carbomethoxymethyl-7-hydroxy-2-pentylchromone (3a), 5-carboethoxymethyl-4',7-dihydroxyflavone (3b) and their derivatives (3c-t), evaluated for their antimicrobial, antioxidant and anticancer activities. Most of the synthesized compounds exhibited antimicrobial activity against the tested microbial strains and some of these compounds were found to be more potent as compared to the standard drugs like neomycin and luteolin. Interestingly, some of these synthesized compounds also showed moderate antioxidant property.
|
Cytotoxicity against TRAIL-resistant human AGS cells assessed as inhibition of cell viability at 17.5 uM after 24 hrs by fluorescence assay in presence of 100 ng/ml TRAIL relative to in absence of TRAIL
|
Homo sapiens
|
48.0
%
|
|
Journal : J. Nat. Prod.
Title : Eudesmane-type sesquiterpenoid and guaianolides from Kandelia candel in a screening program for compounds to overcome TRAIL resistance.
Year : 2012
Volume : 75
Issue : 8
First Page : 1431
Last Page : 1435
Authors : Minakawa T, Toume K, Arai MA, Sadhu SK, Ahmed F, Ishibashi M.
Abstract : In a screening program for natural products that can overcome TRAIL resistance, a new eudesmane-type sesquiterpenoid (1), three new guaianolides, mehirugins A-C (2-4), and two known guaianolides (5 and 6) were isolated from a MeOH extract of Kandelia candel leaves. Compounds 1 and 3-6 in combination with TRAIL showed cytotoxic activity in sensitizing TRAIL-resistant human gastric adenocarcinoma cells.
|
Inhibition of electric eel AChE at 2 mg/ml by Ellman's method
|
Electrophorus electricus
|
13.58
%
|
|
Journal : Bioorg. Med. Chem.
Title : Exploration of natural compounds as sources of new bifunctional scaffolds targeting cholinesterases and beta amyloid aggregation: the case of chelerythrine.
Year : 2012
Volume : 20
Issue : 22
First Page : 6669
Last Page : 6679
Authors : Brunhofer G, Fallarero A, Karlsson D, Batista-Gonzalez A, Shinde P, Gopi Mohan C, Vuorela P.
Abstract : The presented project started by screening a library consisting of natural and natural based compounds for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity. Active compounds were chemically clustered into groups and further tested on the human cholinesterases isoforms. The aim of the presented study was to identify compounds that could be used as leads to target two key mechanisms associated with the AD's pathogenesis simultaneously: cholinergic depletion and beta amyloid (Aβ) aggregation. Berberin, palmatine and chelerythrine, chemically clustered in the so-called isoquinoline group, showed promising cholinesterase inhibitory activity and were therefore further investigated. Moreover, the compounds demonstrated moderate to good inhibition of Aβ aggregation as well as the ability to disaggregate already preformed Aβ aggregates in an experimental set-up using HFIP as promotor of Aβ aggregates. Analysis of the kinetic mechanism of the AChE inhibition revealed chelerythrine as a mixed inhibitor. Using molecular docking studies, it was further proven that chelerythrine binds on both the catalytic site and the peripheral anionic site (PAS) of the AChE. In view of this, we went on to investigate its effect on inhibiting Aβ aggregation stimulated by AChE. Chelerythrine showed inhibition of fibril formation in the same range as propidium iodide. This approach enabled for the first time to identify a cholinesterase inhibitor of natural origin-chelerythrine-acting on AChE and BChE with a dual ability to inhibit Aβ aggregation as well as to disaggregate preformed Aβ aggregates. This compound could be an excellent starting point paving the way to develop more successful anti-AD drugs.
|
Inhibition of horse BChE at 2 mg/ml by Ellman's method
|
Equus caballus
|
0.42
%
|
|
Journal : Bioorg. Med. Chem.
Title : Exploration of natural compounds as sources of new bifunctional scaffolds targeting cholinesterases and beta amyloid aggregation: the case of chelerythrine.
Year : 2012
Volume : 20
Issue : 22
First Page : 6669
Last Page : 6679
Authors : Brunhofer G, Fallarero A, Karlsson D, Batista-Gonzalez A, Shinde P, Gopi Mohan C, Vuorela P.
Abstract : The presented project started by screening a library consisting of natural and natural based compounds for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity. Active compounds were chemically clustered into groups and further tested on the human cholinesterases isoforms. The aim of the presented study was to identify compounds that could be used as leads to target two key mechanisms associated with the AD's pathogenesis simultaneously: cholinergic depletion and beta amyloid (Aβ) aggregation. Berberin, palmatine and chelerythrine, chemically clustered in the so-called isoquinoline group, showed promising cholinesterase inhibitory activity and were therefore further investigated. Moreover, the compounds demonstrated moderate to good inhibition of Aβ aggregation as well as the ability to disaggregate already preformed Aβ aggregates in an experimental set-up using HFIP as promotor of Aβ aggregates. Analysis of the kinetic mechanism of the AChE inhibition revealed chelerythrine as a mixed inhibitor. Using molecular docking studies, it was further proven that chelerythrine binds on both the catalytic site and the peripheral anionic site (PAS) of the AChE. In view of this, we went on to investigate its effect on inhibiting Aβ aggregation stimulated by AChE. Chelerythrine showed inhibition of fibril formation in the same range as propidium iodide. This approach enabled for the first time to identify a cholinesterase inhibitor of natural origin-chelerythrine-acting on AChE and BChE with a dual ability to inhibit Aβ aggregation as well as to disaggregate preformed Aβ aggregates. This compound could be an excellent starting point paving the way to develop more successful anti-AD drugs.
|
Inhibition of alpha-glucosidase (unknown origin) using para-nitrophenyl-alpha-D-glucopyranoside as substrate incubated at 50 to 300 ug/ml for 15 min prior to substrate addition measured after 15 min by spectrophotometric analysis
|
Homo sapiens
|
99.89
%
|
|
Journal : Med Chem Res
Title : Antioxidant and -glucosidase inhibitory compounds from Pimpinella candolleana Wight et Arn.
Year : 2012
Volume : 21
Issue : 12
First Page : 4324
Last Page : 4329
Authors : Chang X, Kang W
|
Antioxidant activity assessed as as DPPH radical scavenging activity after 30 min by spectrophotometry
|
None
|
0.99
ug.mL-1
|
|
Journal : Med Chem Res
Title : Antioxidant and -glucosidase inhibitory compounds from Pimpinella candolleana Wight et Arn.
Year : 2012
Volume : 21
Issue : 12
First Page : 4324
Last Page : 4329
Authors : Chang X, Kang W
|
Inhibition of alpha-glucosidase (unknown origin) using para-nitrophenyl-alpha-D-glucopyranoside as substrate incubated for 15 min prior to substrate addition measured after 15 min by spectrophotometric analysis
|
Homo sapiens
|
5.96
ug.mL-1
|
|
Journal : Med Chem Res
Title : Antioxidant and -glucosidase inhibitory compounds from Pimpinella candolleana Wight et Arn.
Year : 2012
Volume : 21
Issue : 12
First Page : 4324
Last Page : 4329
Authors : Chang X, Kang W
|
Antifungal activity against Verticillium dahliae assessed as inhibition of mycelial radial growth measured after 350 hr
|
Verticillium dahliae
|
7.0
ug.mL-1
|
|
Journal : J Agric Food Chem
Title : Dysfunctionality of the xylem in Olea europaea L. Plants associated with the infection process by Verticillium dahliae Kleb. Role of phenolic compounds in plant defense mechanism.
Year : 2007
Volume : 55
Issue : 9
First Page : 3373
Last Page : 3377
Authors : Báidez AG, Gómez P, Del Río JA, Ortuño A.
Abstract : Xylem ultrastructural modification and the possible participation of phenolic compounds in the natural defense or resistance mechanisms of olive plants infected with Verticillium dahliae Kleb. were studied. Microscopic study showed that the mycelium propagated and passed from one element to another through the pit. The formation of tyloses and aggregates contributed to obstruction of the xylem lumen. In vivo changes in the levels of these phenolic compounds in infected olive plants and their antifungal activity against Verticillium dahliae Kleb., as revealed by in vitro study, strongly suggest that they are involved in natural defense or resistance mechanisms in this plant material, the most active being quercetin and luteolin aglycons, followed by rutin, oleuropein, luteolin-7-glucoside, tyrosol, p-coumaric acid, and catechin. .
|
Antiamoebic activity against Entamoeba histolytica
|
Entamoeba histolytica
|
17.8
ug.mL-1
|
|
Journal : Med Chem Res
Title : Exploring QSAR of antiamoebic agents of isolated natural products by MLR, ANN, and RTO
Year : 2012
Volume : 21
Issue : 9
First Page : 2501
Last Page : 2516
Authors : Ramirez-Galicia G, Martinez-Pacheco H, Garduno-Juarez R, Deeb O
|
Insecticidal activity against third-instar Spodoptera exigua larvae assessed as inhibition of body weight increase at 16 g/l measured from 24 hr to 48 hr
|
Spodoptera exigua
|
66.85
%
|
|
Journal : J Pesticide Sci
Title : The effects of luteolin on phenoloxidase and the growth of Spodoptera exigua (Hubner) larvae (Lepidoptera: Noctuidae)
Year : 2010
Volume : 35
Issue : 4
First Page : 483
Last Page : 487
Authors : Wang S, Liu W, Xue C, Luo W
|
Insecticidal activity against third-instar Spodoptera exigua larvae assessed as inhibition of body weight increase at 8 g/l measured from 24 hr to 48 hr
|
Spodoptera exigua
|
56.82
%
|
|
Journal : J Pesticide Sci
Title : The effects of luteolin on phenoloxidase and the growth of Spodoptera exigua (Hubner) larvae (Lepidoptera: Noctuidae)
Year : 2010
Volume : 35
Issue : 4
First Page : 483
Last Page : 487
Authors : Wang S, Liu W, Xue C, Luo W
|
Insecticidal activity against third-instar Spodoptera exigua larvae assessed as inhibition of body weight increase at 4 g/l measured from 24 hr to 48 hr
|
Spodoptera exigua
|
49.63
%
|
|
Journal : J Pesticide Sci
Title : The effects of luteolin on phenoloxidase and the growth of Spodoptera exigua (Hubner) larvae (Lepidoptera: Noctuidae)
Year : 2010
Volume : 35
Issue : 4
First Page : 483
Last Page : 487
Authors : Wang S, Liu W, Xue C, Luo W
|
Insecticidal activity against third-instar Spodoptera exigua larvae assessed as inhibition of body weight increase at 2 g/l measured from 24 hr to 48 hr
|
Spodoptera exigua
|
42.68
%
|
|
Journal : J Pesticide Sci
Title : The effects of luteolin on phenoloxidase and the growth of Spodoptera exigua (Hubner) larvae (Lepidoptera: Noctuidae)
Year : 2010
Volume : 35
Issue : 4
First Page : 483
Last Page : 487
Authors : Wang S, Liu W, Xue C, Luo W
|
Insecticidal activity against third-instar Spodoptera exigua larvae assessed as inhibition of body weight increase at 1 g/l measured from 24 hr to 48 hr
|
Spodoptera exigua
|
37.96
%
|
|
Journal : J Pesticide Sci
Title : The effects of luteolin on phenoloxidase and the growth of Spodoptera exigua (Hubner) larvae (Lepidoptera: Noctuidae)
Year : 2010
Volume : 35
Issue : 4
First Page : 483
Last Page : 487
Authors : Wang S, Liu W, Xue C, Luo W
|
Antinociceptive activity Swiss albino Mus musculus (mouse) assessed as inhibition of formalin-induced paw licking at 10 mg/kg, po administered 60 min prior to formalin-challenge measured from 15 to 30 min relative to control
|
Mus musculus
|
48.64
%
|
|
Journal : Med Chem Res
Title : Bioactivity guided isolation of antiinflammatory, analgesic, and antipyretic constituents from the leaves of Pedilanthus tithymaloides (L.)
Year : 2013
Volume : 22
Issue : 9
First Page : 4347
Last Page : 4359
Authors : Ghosh S, Chattopadhyay D, Mandal A, Kaity S, Samanta A
|
Antinociceptive activity Swiss albino Mus musculus (mouse) assessed as inhibition of formalin-induced paw licking at 10 mg/kg, po administered 60 min prior to formalin-challenge measured up to 5 min relative to control
|
Mus musculus
|
40.31
%
|
|
Journal : Med Chem Res
Title : Bioactivity guided isolation of antiinflammatory, analgesic, and antipyretic constituents from the leaves of Pedilanthus tithymaloides (L.)
Year : 2013
Volume : 22
Issue : 9
First Page : 4347
Last Page : 4359
Authors : Ghosh S, Chattopadhyay D, Mandal A, Kaity S, Samanta A
|
Antinociceptive activity in Swiss albino Mus musculus (mouse) assessed as inhibition of acetic acid-induced writhing at 10 mg/kg, po administered 1 hr prior to acetic acid-challenge measured up to 20 min relative to control
|
Mus musculus
|
55.35
%
|
|
Journal : Med Chem Res
Title : Bioactivity guided isolation of antiinflammatory, analgesic, and antipyretic constituents from the leaves of Pedilanthus tithymaloides (L.)
Year : 2013
Volume : 22
Issue : 9
First Page : 4347
Last Page : 4359
Authors : Ghosh S, Chattopadhyay D, Mandal A, Kaity S, Samanta A
|
Anti-inflammatory activity in Swiss albino Mus musculus (mouse) assessed as inhibition of cotton pellet-induced granuloma formation at 10 mg/kg, po administered QD for 5 days measured at 1 hr post-last dose relative to control
|
Mus musculus
|
36.98
%
|
|
Journal : Med Chem Res
Title : Bioactivity guided isolation of antiinflammatory, analgesic, and antipyretic constituents from the leaves of Pedilanthus tithymaloides (L.)
Year : 2013
Volume : 22
Issue : 9
First Page : 4347
Last Page : 4359
Authors : Ghosh S, Chattopadhyay D, Mandal A, Kaity S, Samanta A
|
Anti-inflammatory activity in Swiss albino Mus musculus (mouse) assessed as inhibition of carrageenan-induced paw edema at 10 mg/kg, ip administered 30 min prior to carrageenan-challenge measured after 5 hr relative to control
|
Mus musculus
|
50.0
%
|
|
Journal : Med Chem Res
Title : Bioactivity guided isolation of antiinflammatory, analgesic, and antipyretic constituents from the leaves of Pedilanthus tithymaloides (L.)
Year : 2013
Volume : 22
Issue : 9
First Page : 4347
Last Page : 4359
Authors : Ghosh S, Chattopadhyay D, Mandal A, Kaity S, Samanta A
|
Inhibition of recombinant FLT3 (unknown origin) by TR-FRET assay
|
Homo sapiens
|
830.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Flavonoids as receptor tyrosine kinase FLT3 inhibitors.
Year : 2013
Volume : 23
Issue : 6
First Page : 1768
Last Page : 1770
Authors : Chin YW, Kong JY, Han SY.
Abstract : The Fms-like tyrosine kinase 3 (FLT3), a receptor tyrosine kinase, is involved in the proliferation, differentiation and apoptosis of hematopoietic cells. FLT3 is highly overexpressed in acute myeloid leukemia (AML) of the majority of patients. Screening for flavonoids including flavones, flavanones, flavonols, and flavanonols disclosed that luteolin was potent FLT3 enzyme inhibitor. Furthermore, luteolin suppressed cell proliferation in MV4;11 cells with constitutively activated FLT3.
|
Antioxidant activity assessed as inhibition of lipid peroxidation activity after 15 mins by MDA assay
|
None
|
149.7
ug.mL-1
|
|
Journal : Eur. J. Med. Chem.
Title : Novel 2-(2,4-dioxo-1,3-thiazolidin-5-yl)acetamides as antioxidant and/or anti-inflammatory compounds.
Year : 2013
Volume : 66
First Page : 305
Last Page : 313
Authors : Koppireddi S, Komsani JR, Avula S, Pombala S, Vasamsetti S, Kotamraju S, Yadla R.
Abstract : A series of novel N-(4-aryl-1,3-thiazol-2-yl)-2-(2,4-dioxo-1,3-thiazolidin-5-yl)acetamides (4a-k) and N-(1,3-benzothiazol-2-yl)-2-(2,4-dioxo-1,3-thiazolidin-5-yl)acetamide derivatives (4l-o) are synthesized and evaluated for their anti-inflammatory and antioxidant activity (DPPH radical scavenging, superoxide anion scavenging, lipid peroxide inhibition, erythrocyte hemolytic inhibition). Compounds 4k and 4l have exhibited good antioxidant activity in four assays, while compounds 4c, 4d, 4m, 4n and 4o have shown good DPPH radical scavenging efficacy. Compounds 4a, 4h, 4i, 4k, 4m and 4n have possessed excellent anti-inflammatory activity. N-[4-(o-methoxyphenyl)-1,3-thiazol-2-yl]-2-(2,4-dioxo-1,3-thiazolidin-5-yl)acetamide (4k) and N-(6-nitro-/methoxy-1,3-benzothiazol-2-yl)-2-(2,4-dioxo-1,3-thiazolidin-5-yl)acetamide (4m and 4n) have exhibited both antioxidant and anti-inflammatory activities.
|
Hemolysis of human erythrocytes after 30 mins by spectrophotometry
|
Homo sapiens
|
107.28
ug.mL-1
|
|
Journal : Eur. J. Med. Chem.
Title : Novel 2-(2,4-dioxo-1,3-thiazolidin-5-yl)acetamides as antioxidant and/or anti-inflammatory compounds.
Year : 2013
Volume : 66
First Page : 305
Last Page : 313
Authors : Koppireddi S, Komsani JR, Avula S, Pombala S, Vasamsetti S, Kotamraju S, Yadla R.
Abstract : A series of novel N-(4-aryl-1,3-thiazol-2-yl)-2-(2,4-dioxo-1,3-thiazolidin-5-yl)acetamides (4a-k) and N-(1,3-benzothiazol-2-yl)-2-(2,4-dioxo-1,3-thiazolidin-5-yl)acetamide derivatives (4l-o) are synthesized and evaluated for their anti-inflammatory and antioxidant activity (DPPH radical scavenging, superoxide anion scavenging, lipid peroxide inhibition, erythrocyte hemolytic inhibition). Compounds 4k and 4l have exhibited good antioxidant activity in four assays, while compounds 4c, 4d, 4m, 4n and 4o have shown good DPPH radical scavenging efficacy. Compounds 4a, 4h, 4i, 4k, 4m and 4n have possessed excellent anti-inflammatory activity. N-[4-(o-methoxyphenyl)-1,3-thiazol-2-yl]-2-(2,4-dioxo-1,3-thiazolidin-5-yl)acetamide (4k) and N-(6-nitro-/methoxy-1,3-benzothiazol-2-yl)-2-(2,4-dioxo-1,3-thiazolidin-5-yl)acetamide (4m and 4n) have exhibited both antioxidant and anti-inflammatory activities.
|
Antioxidant activity assessed as DPPH scavenging activity after 30 mins by UV-visible spectrophotometry
|
None
|
44.18
ug.mL-1
|
|
Journal : Eur. J. Med. Chem.
Title : Novel 2-(2,4-dioxo-1,3-thiazolidin-5-yl)acetamides as antioxidant and/or anti-inflammatory compounds.
Year : 2013
Volume : 66
First Page : 305
Last Page : 313
Authors : Koppireddi S, Komsani JR, Avula S, Pombala S, Vasamsetti S, Kotamraju S, Yadla R.
Abstract : A series of novel N-(4-aryl-1,3-thiazol-2-yl)-2-(2,4-dioxo-1,3-thiazolidin-5-yl)acetamides (4a-k) and N-(1,3-benzothiazol-2-yl)-2-(2,4-dioxo-1,3-thiazolidin-5-yl)acetamide derivatives (4l-o) are synthesized and evaluated for their anti-inflammatory and antioxidant activity (DPPH radical scavenging, superoxide anion scavenging, lipid peroxide inhibition, erythrocyte hemolytic inhibition). Compounds 4k and 4l have exhibited good antioxidant activity in four assays, while compounds 4c, 4d, 4m, 4n and 4o have shown good DPPH radical scavenging efficacy. Compounds 4a, 4h, 4i, 4k, 4m and 4n have possessed excellent anti-inflammatory activity. N-[4-(o-methoxyphenyl)-1,3-thiazol-2-yl]-2-(2,4-dioxo-1,3-thiazolidin-5-yl)acetamide (4k) and N-(6-nitro-/methoxy-1,3-benzothiazol-2-yl)-2-(2,4-dioxo-1,3-thiazolidin-5-yl)acetamide (4m and 4n) have exhibited both antioxidant and anti-inflammatory activities.
|
Antioxidant activity assessed as superoxide radical scavenging activity after 5 mins by spectrophotometry
|
None
|
31.01
ug.mL-1
|
|
Journal : Eur. J. Med. Chem.
Title : Novel 2-(2,4-dioxo-1,3-thiazolidin-5-yl)acetamides as antioxidant and/or anti-inflammatory compounds.
Year : 2013
Volume : 66
First Page : 305
Last Page : 313
Authors : Koppireddi S, Komsani JR, Avula S, Pombala S, Vasamsetti S, Kotamraju S, Yadla R.
Abstract : A series of novel N-(4-aryl-1,3-thiazol-2-yl)-2-(2,4-dioxo-1,3-thiazolidin-5-yl)acetamides (4a-k) and N-(1,3-benzothiazol-2-yl)-2-(2,4-dioxo-1,3-thiazolidin-5-yl)acetamide derivatives (4l-o) are synthesized and evaluated for their anti-inflammatory and antioxidant activity (DPPH radical scavenging, superoxide anion scavenging, lipid peroxide inhibition, erythrocyte hemolytic inhibition). Compounds 4k and 4l have exhibited good antioxidant activity in four assays, while compounds 4c, 4d, 4m, 4n and 4o have shown good DPPH radical scavenging efficacy. Compounds 4a, 4h, 4i, 4k, 4m and 4n have possessed excellent anti-inflammatory activity. N-[4-(o-methoxyphenyl)-1,3-thiazol-2-yl]-2-(2,4-dioxo-1,3-thiazolidin-5-yl)acetamide (4k) and N-(6-nitro-/methoxy-1,3-benzothiazol-2-yl)-2-(2,4-dioxo-1,3-thiazolidin-5-yl)acetamide (4m and 4n) have exhibited both antioxidant and anti-inflammatory activities.
|
Inhibition of human recombinant aldose reductase
|
Homo sapiens
|
600.0
nM
|
|
Journal : Bioorg. Med. Chem.
Title : Synthesis of organic nitrates of luteolin as a novel class of potent aldose reductase inhibitors.
Year : 2013
Volume : 21
Issue : 14
First Page : 4301
Last Page : 4310
Authors : Wang QQ, Cheng N, Zheng XW, Peng SM, Zou XQ.
Abstract : Aldose reductase (AR) plays an important role in the design of drugs that prevent and treat diabetic complications. Aldose reductase inhibitors (ARIs) have received significant attentions as potent therapeutic drugs. Based on combination principles, three series of luteolin derivatives were synthesised and evaluated for their AR inhibitory activity and nitric oxide (NO)-releasing capacity in vitro. Eighteen compounds were found to be potent ARIs with IC50 values ranging from (0.099±0.008) μM to (2.833±0.102) μM. O(7)-Nitrooxyethyl-O(3'),O(4')-ethylidene luteolin (La1) showed the most potent AR inhibitory activity [IC50=(0.099±0.008) μM]. All organic nitrate derivatives released low concentrations of NO in the presence of l-cysteine. Structure-activity relationship studies suggested that introduction of an NO donor, protection of the catechol structure, and the ether chain of a 2-carbon spacer as a coupling chain on the luteolin scaffold all help increase the AR inhibitory activity of the resulting compound. This class of NO-donor luteolin derivatives as efficient ARIs offer a new concept for the development and design of new drug for preventive and therapeutic drugs for diabetic complications.
|
Inhibition of bovine lens aldose reductase using DL-glyceraldehyde as substrate assessed as NADPH oxidation measured for 10 mins by spectrophotometric analysis
|
Bos taurus
|
754.0
nM
|
|
Journal : Bioorg. Med. Chem.
Title : Synthesis of organic nitrates of luteolin as a novel class of potent aldose reductase inhibitors.
Year : 2013
Volume : 21
Issue : 14
First Page : 4301
Last Page : 4310
Authors : Wang QQ, Cheng N, Zheng XW, Peng SM, Zou XQ.
Abstract : Aldose reductase (AR) plays an important role in the design of drugs that prevent and treat diabetic complications. Aldose reductase inhibitors (ARIs) have received significant attentions as potent therapeutic drugs. Based on combination principles, three series of luteolin derivatives were synthesised and evaluated for their AR inhibitory activity and nitric oxide (NO)-releasing capacity in vitro. Eighteen compounds were found to be potent ARIs with IC50 values ranging from (0.099±0.008) μM to (2.833±0.102) μM. O(7)-Nitrooxyethyl-O(3'),O(4')-ethylidene luteolin (La1) showed the most potent AR inhibitory activity [IC50=(0.099±0.008) μM]. All organic nitrate derivatives released low concentrations of NO in the presence of l-cysteine. Structure-activity relationship studies suggested that introduction of an NO donor, protection of the catechol structure, and the ether chain of a 2-carbon spacer as a coupling chain on the luteolin scaffold all help increase the AR inhibitory activity of the resulting compound. This class of NO-donor luteolin derivatives as efficient ARIs offer a new concept for the development and design of new drug for preventive and therapeutic drugs for diabetic complications.
|
Inhibition of MPO release in zymosan-stimulated human neutrophils by luminol-dependent chemiluminescence assay
|
Homo sapiens
|
100.0
%
|
|
Journal : Eur. J. Med. Chem.
Title : Modulation of human neutrophils' oxidative burst by flavonoids.
Year : 2013
Volume : 67
First Page : 280
Last Page : 292
Authors : Ribeiro D, Freitas M, Tomé SM, Silva AM, Porto G, Fernandes E.
Abstract : Inflammation is a normal response towards tissue injury, but may become deleterious to the organism if uncontrolled. The overproduction of reactive species during the inflammatory process may cause or magnify the damage at inflammatory sites. Flavonoids have been suggested as therapeutic agents to avoid such damage, as these compounds exhibit anti-inflammatory activity, through the modulation of oxidative stress and signalling pathways. Both effects may attenuate neutrophils' activities at inflammatory sites. In this study, we investigated the structure/activity relationship of a series of flavonoids on the oxidative burst of human neutrophils in vitro, as a measure of its anti-inflammatory potential. Neutrophils were stimulated with phorbol-12-myristate-13-acetate, and fluorescence and chemiluminescence techniques were used to evaluate the generation of reactive oxygen species. All the tested flavonoids revealed the ability to modulate the neutrophil's oxidative burst. From the obtained results, the pivotal role of the catechol group in the B-ring was evidenced as well as the minor importance of the hydroxylations in the A-ring, which did not appear to be determinant for the activity, although clearly influencing the lipophilicity of the tested flavonoids. It is also clarified the importance of the methylation in the OH group at the B-ring catechol moiety. In conclusion, the obtained results uncover new possible strategies for the resolution of inflammatory processes, using flavonoids to modulate neutrophil's oxidative burst.
|
Inhibition of oxidative burst in PMA-stimulated human neutrophils assessed as inhibition of HOCl-induced oxidation of APF after 6 mins by fluorescence assay
|
Homo sapiens
|
900.0
nM
|
|
Journal : Eur. J. Med. Chem.
Title : Modulation of human neutrophils' oxidative burst by flavonoids.
Year : 2013
Volume : 67
First Page : 280
Last Page : 292
Authors : Ribeiro D, Freitas M, Tomé SM, Silva AM, Porto G, Fernandes E.
Abstract : Inflammation is a normal response towards tissue injury, but may become deleterious to the organism if uncontrolled. The overproduction of reactive species during the inflammatory process may cause or magnify the damage at inflammatory sites. Flavonoids have been suggested as therapeutic agents to avoid such damage, as these compounds exhibit anti-inflammatory activity, through the modulation of oxidative stress and signalling pathways. Both effects may attenuate neutrophils' activities at inflammatory sites. In this study, we investigated the structure/activity relationship of a series of flavonoids on the oxidative burst of human neutrophils in vitro, as a measure of its anti-inflammatory potential. Neutrophils were stimulated with phorbol-12-myristate-13-acetate, and fluorescence and chemiluminescence techniques were used to evaluate the generation of reactive oxygen species. All the tested flavonoids revealed the ability to modulate the neutrophil's oxidative burst. From the obtained results, the pivotal role of the catechol group in the B-ring was evidenced as well as the minor importance of the hydroxylations in the A-ring, which did not appear to be determinant for the activity, although clearly influencing the lipophilicity of the tested flavonoids. It is also clarified the importance of the methylation in the OH group at the B-ring catechol moiety. In conclusion, the obtained results uncover new possible strategies for the resolution of inflammatory processes, using flavonoids to modulate neutrophil's oxidative burst.
|
Antiviral activity against HIV-1 3B infected in human C8166 cells assessed as inhibition of virus-induced cytopathogenicity by measuring syncytial cell number after 3 days by inverted microscopic analysis
|
Human immunodeficiency virus 1
|
2.48
ug.mL-1
|
|
Journal : Bioorg. Med. Chem.
Title : Design and discovery of flavonoid-based HIV-1 integrase inhibitors targeting both the active site and the interaction with LEDGF/p75.
Year : 2014
Volume : 22
Issue : 12
First Page : 3146
Last Page : 3158
Authors : Li BW, Zhang FH, Serrao E, Chen H, Sanchez TW, Yang LM, Neamati N, Zheng YT, Wang H, Long YQ.
Abstract : HIV integrase (IN) is an essential enzyme for the viral replication. Currently, three IN inhibitors have been approved for treating HIV-1 infection. All three drugs selectively inhibit the strand transfer reaction by chelating a divalent metal ion in the enzyme active site. Flavonoids are a well-known class of natural products endowed with versatile biological activities. Their β-ketoenol or catechol structures can serve as a metal chelation motif and be exploited for the design of novel IN inhibitors. Using the metal chelation as a common pharmacophore, we introduced appropriate hydrophobic moieties into the flavonol core to design natural product-based novel IN inhibitors. We developed selective and efficient syntheses to generate a series of mono 3/5/7/3'/4'-substituted flavonoid derivatives. Most of these new compounds showed excellent HIV-1 IN inhibitory activity in enzyme-based assays and protected against HIV-1 infection in cell-based assays. The 7-morpholino substituted 7c showed effective antiviral activity (EC50=0.826 μg/mL) and high therapeutic index (TI>242). More significantly, these hydroxyflavones block the IN-LEDGF/p75 interaction with low- to sub-micromolar IC50 values and represent a novel scaffold to design new generation of drugs simultaneously targeting the catalytic site as well as protein-protein interaction domains.
|
Inhibition of His6-tagged HIV-1 integrase assessed as decrease in integrase-Flag-LEDGF/p75 interaction preincubated with enzyme for 30 mins followed by addition of Flag-LEDGF/p75 for 1 hr by AlphaScreen assay
|
Human immunodeficiency virus 1
|
450.0
nM
|
|
Journal : Bioorg. Med. Chem.
Title : Design and discovery of flavonoid-based HIV-1 integrase inhibitors targeting both the active site and the interaction with LEDGF/p75.
Year : 2014
Volume : 22
Issue : 12
First Page : 3146
Last Page : 3158
Authors : Li BW, Zhang FH, Serrao E, Chen H, Sanchez TW, Yang LM, Neamati N, Zheng YT, Wang H, Long YQ.
Abstract : HIV integrase (IN) is an essential enzyme for the viral replication. Currently, three IN inhibitors have been approved for treating HIV-1 infection. All three drugs selectively inhibit the strand transfer reaction by chelating a divalent metal ion in the enzyme active site. Flavonoids are a well-known class of natural products endowed with versatile biological activities. Their β-ketoenol or catechol structures can serve as a metal chelation motif and be exploited for the design of novel IN inhibitors. Using the metal chelation as a common pharmacophore, we introduced appropriate hydrophobic moieties into the flavonol core to design natural product-based novel IN inhibitors. We developed selective and efficient syntheses to generate a series of mono 3/5/7/3'/4'-substituted flavonoid derivatives. Most of these new compounds showed excellent HIV-1 IN inhibitory activity in enzyme-based assays and protected against HIV-1 infection in cell-based assays. The 7-morpholino substituted 7c showed effective antiviral activity (EC50=0.826 μg/mL) and high therapeutic index (TI>242). More significantly, these hydroxyflavones block the IN-LEDGF/p75 interaction with low- to sub-micromolar IC50 values and represent a novel scaffold to design new generation of drugs simultaneously targeting the catalytic site as well as protein-protein interaction domains.
|
Inhibition of NO production in LPS-stimulated mouse RAW264.7 cells pre-incubated for 2 hrs before LPS stimulation for 24 hrs by Griess assay method
|
Mus musculus
|
210.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : New guaiane sesquiterpenes from Artemisia rupestris and their inhibitory effects on nitric oxide production.
Year : 2014
Volume : 24
Issue : 18
First Page : 4435
Last Page : 4438
Authors : Hou J, Dong H, Yan M, Zhu F, Zhang X, Wang H, Ye W, Li P.
Abstract : Phytochemical investigation of the ethanol extract of the aerial parts of Artemisia rupestris resulted in the isolation of three new guaiane sesquiterpenes, (1R,7R,10S)-1-hydroxy-3-oxoguaia-4,11(13)-dien-12-oic acid (1), (1R,7R,10S)-10-hydroxy-3-oxoguaia-4,11(13)-dien-12-oic acid (2), pechueloic acid 12-O-β-d-glucopyranoside (3), together with 12 known compounds (4-15). The structures of these new compounds were established on the basis of extensive spectroscopic analysis and electronic circular dichroism (ECD) calculation. All isolates were evaluated for their in vitro inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages cells, and the structure-activity relationships were also discussed.
|
Inhibition of alpha glucosidase (unknown origin) at 0.5 mg/ml
|
Homo sapiens
|
36.0
%
|
|
Journal : Eur. J. Med. Chem.
Title : Flavones: an important scaffold for medicinal chemistry.
Year : 2014
Volume : 84
First Page : 206
Last Page : 239
Authors : Singh M, Kaur M, Silakari O.
Abstract : Flavones have antioxidant, anti-proliferative, anti-tumor, anti-microbial, estrogenic, acetyl cholinesterase, anti-inflammatory activities and are also used in cancer, cardiovascular disease, neurodegenerative disorders, etc. Also, flavonoids are found to have an effect on several mammalian enzymes like protein kinases that regulate multiple cell signaling pathways and alterations in multiple cellular signaling pathways are frequently found in many diseases. Flavones have been an indispensable anchor for the development of new therapeutic agents. The majority of metabolic diseases are speculated to originate from oxidative stress, and it is therefore significant that recent studies have shown the positive effect of flavones on diseases related to oxidative stress. Due to the wide range of biological activities of flavones, their structure-activity relationships have generated interest among medicinal chemists. The outstanding development of flavones derivatives in diverse diseases in very short span of time proves its magnitude for medicinal chemistry research. The present review gives detail about the structural requirement of flavone derivatives for various pharmacological activities. This information may provide an opportunity to scientists of medicinal chemistry discipline to design selective, optimize as well as poly-functional flavone derivatives for the treatment of multi-factorial diseases.
|
Inhibition of melanogenesis in theophylline-stimulated mouse B16-4A5 cells at 1 uM after 72 hrs by microplate reader analysis relative to control
|
Mus musculus
|
6.2
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Inhibitors of melanogenesis in B16 melanoma 4A5 cells from flower buds of Lawsonia inermis (Henna).
Year : 2015
Volume : 25
Issue : 13
First Page : 2702
Last Page : 2706
Authors : Nakashima S, Oda Y, Nakamura S, Liu J, Onishi K, Kawabata M, Miki H, Himuro Y, Yoshikawa M, Matsuda H.
Abstract : The methanolic extract of Lawsonia inermis L. (henna) showed significant inhibitory activity toward melanogenesis in B16 melanoma 4A5 cells. Among the constituents isolated from the methanolic extract, luteolin, quercetin, and (±)-eriodictyol showed stronger inhibitory activity than the reference compound, arbutin. Several structure-activity relationships of the flavonoids were suggested, and OGlc<H=OH at the 3-position, OGlc<OH at the 4'-position, and the double bond between the 2- and 3-positions were important. The active constituents suppressed tyrosinase, tyrosinase related protein (TRP)-1, and TRP-2 mRNA expression. The suppression was considered as one of the mechanisms of action. Furthermore, the methanolic extract and several constituents, including luteoloside and spiraeoside, showed anti-plasmin activity, which is considered to play a key role in UV-stimulated melanogenesis in human skin.
|
Inhibition of melanogenesis in theophylline-stimulated mouse B16-4A5 cells at 3 uM after 72 hrs by microplate reader analysis relative to control
|
Mus musculus
|
13.5
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Inhibitors of melanogenesis in B16 melanoma 4A5 cells from flower buds of Lawsonia inermis (Henna).
Year : 2015
Volume : 25
Issue : 13
First Page : 2702
Last Page : 2706
Authors : Nakashima S, Oda Y, Nakamura S, Liu J, Onishi K, Kawabata M, Miki H, Himuro Y, Yoshikawa M, Matsuda H.
Abstract : The methanolic extract of Lawsonia inermis L. (henna) showed significant inhibitory activity toward melanogenesis in B16 melanoma 4A5 cells. Among the constituents isolated from the methanolic extract, luteolin, quercetin, and (±)-eriodictyol showed stronger inhibitory activity than the reference compound, arbutin. Several structure-activity relationships of the flavonoids were suggested, and OGlc<H=OH at the 3-position, OGlc<OH at the 4'-position, and the double bond between the 2- and 3-positions were important. The active constituents suppressed tyrosinase, tyrosinase related protein (TRP)-1, and TRP-2 mRNA expression. The suppression was considered as one of the mechanisms of action. Furthermore, the methanolic extract and several constituents, including luteoloside and spiraeoside, showed anti-plasmin activity, which is considered to play a key role in UV-stimulated melanogenesis in human skin.
|
Inhibition of melanogenesis in theophylline-stimulated mouse B16-4A5 cells at 10 uM after 72 hrs by microplate reader analysis relative to control
|
Mus musculus
|
38.1
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Inhibitors of melanogenesis in B16 melanoma 4A5 cells from flower buds of Lawsonia inermis (Henna).
Year : 2015
Volume : 25
Issue : 13
First Page : 2702
Last Page : 2706
Authors : Nakashima S, Oda Y, Nakamura S, Liu J, Onishi K, Kawabata M, Miki H, Himuro Y, Yoshikawa M, Matsuda H.
Abstract : The methanolic extract of Lawsonia inermis L. (henna) showed significant inhibitory activity toward melanogenesis in B16 melanoma 4A5 cells. Among the constituents isolated from the methanolic extract, luteolin, quercetin, and (±)-eriodictyol showed stronger inhibitory activity than the reference compound, arbutin. Several structure-activity relationships of the flavonoids were suggested, and OGlc<H=OH at the 3-position, OGlc<OH at the 4'-position, and the double bond between the 2- and 3-positions were important. The active constituents suppressed tyrosinase, tyrosinase related protein (TRP)-1, and TRP-2 mRNA expression. The suppression was considered as one of the mechanisms of action. Furthermore, the methanolic extract and several constituents, including luteoloside and spiraeoside, showed anti-plasmin activity, which is considered to play a key role in UV-stimulated melanogenesis in human skin.
|
Inhibition of melanogenesis in theophylline-stimulated mouse B16-4A5 cells at 30 uM after 72 hrs by microplate reader analysis relative to control
|
Mus musculus
|
76.7
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Inhibitors of melanogenesis in B16 melanoma 4A5 cells from flower buds of Lawsonia inermis (Henna).
Year : 2015
Volume : 25
Issue : 13
First Page : 2702
Last Page : 2706
Authors : Nakashima S, Oda Y, Nakamura S, Liu J, Onishi K, Kawabata M, Miki H, Himuro Y, Yoshikawa M, Matsuda H.
Abstract : The methanolic extract of Lawsonia inermis L. (henna) showed significant inhibitory activity toward melanogenesis in B16 melanoma 4A5 cells. Among the constituents isolated from the methanolic extract, luteolin, quercetin, and (±)-eriodictyol showed stronger inhibitory activity than the reference compound, arbutin. Several structure-activity relationships of the flavonoids were suggested, and OGlc<H=OH at the 3-position, OGlc<OH at the 4'-position, and the double bond between the 2- and 3-positions were important. The active constituents suppressed tyrosinase, tyrosinase related protein (TRP)-1, and TRP-2 mRNA expression. The suppression was considered as one of the mechanisms of action. Furthermore, the methanolic extract and several constituents, including luteoloside and spiraeoside, showed anti-plasmin activity, which is considered to play a key role in UV-stimulated melanogenesis in human skin.
|
Inhibition of mushroom tyrosinase using L-DOPA as substrate assessed as dopaquinone production at 10 uM after 5 mins by microplate reader analysis relative to control
|
Agaricus bisporus
|
11.4
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Inhibitors of melanogenesis in B16 melanoma 4A5 cells from flower buds of Lawsonia inermis (Henna).
Year : 2015
Volume : 25
Issue : 13
First Page : 2702
Last Page : 2706
Authors : Nakashima S, Oda Y, Nakamura S, Liu J, Onishi K, Kawabata M, Miki H, Himuro Y, Yoshikawa M, Matsuda H.
Abstract : The methanolic extract of Lawsonia inermis L. (henna) showed significant inhibitory activity toward melanogenesis in B16 melanoma 4A5 cells. Among the constituents isolated from the methanolic extract, luteolin, quercetin, and (±)-eriodictyol showed stronger inhibitory activity than the reference compound, arbutin. Several structure-activity relationships of the flavonoids were suggested, and OGlc<H=OH at the 3-position, OGlc<OH at the 4'-position, and the double bond between the 2- and 3-positions were important. The active constituents suppressed tyrosinase, tyrosinase related protein (TRP)-1, and TRP-2 mRNA expression. The suppression was considered as one of the mechanisms of action. Furthermore, the methanolic extract and several constituents, including luteoloside and spiraeoside, showed anti-plasmin activity, which is considered to play a key role in UV-stimulated melanogenesis in human skin.
|
Inhibition of mushroom tyrosinase using L-DOPA as substrate assessed as dopaquinone production at 100 uM after 5 mins by microplate reader analysis relative to control
|
Agaricus bisporus
|
33.5
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Inhibitors of melanogenesis in B16 melanoma 4A5 cells from flower buds of Lawsonia inermis (Henna).
Year : 2015
Volume : 25
Issue : 13
First Page : 2702
Last Page : 2706
Authors : Nakashima S, Oda Y, Nakamura S, Liu J, Onishi K, Kawabata M, Miki H, Himuro Y, Yoshikawa M, Matsuda H.
Abstract : The methanolic extract of Lawsonia inermis L. (henna) showed significant inhibitory activity toward melanogenesis in B16 melanoma 4A5 cells. Among the constituents isolated from the methanolic extract, luteolin, quercetin, and (±)-eriodictyol showed stronger inhibitory activity than the reference compound, arbutin. Several structure-activity relationships of the flavonoids were suggested, and OGlc<H=OH at the 3-position, OGlc<OH at the 4'-position, and the double bond between the 2- and 3-positions were important. The active constituents suppressed tyrosinase, tyrosinase related protein (TRP)-1, and TRP-2 mRNA expression. The suppression was considered as one of the mechanisms of action. Furthermore, the methanolic extract and several constituents, including luteoloside and spiraeoside, showed anti-plasmin activity, which is considered to play a key role in UV-stimulated melanogenesis in human skin.
|
Inhibition of plasmin (unknown origin) at 100 uM after 18 hrs by arianor mahogany dye-based fibrin plate assay relative to control
|
Homo sapiens
|
28.7
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Inhibitors of melanogenesis in B16 melanoma 4A5 cells from flower buds of Lawsonia inermis (Henna).
Year : 2015
Volume : 25
Issue : 13
First Page : 2702
Last Page : 2706
Authors : Nakashima S, Oda Y, Nakamura S, Liu J, Onishi K, Kawabata M, Miki H, Himuro Y, Yoshikawa M, Matsuda H.
Abstract : The methanolic extract of Lawsonia inermis L. (henna) showed significant inhibitory activity toward melanogenesis in B16 melanoma 4A5 cells. Among the constituents isolated from the methanolic extract, luteolin, quercetin, and (±)-eriodictyol showed stronger inhibitory activity than the reference compound, arbutin. Several structure-activity relationships of the flavonoids were suggested, and OGlc<H=OH at the 3-position, OGlc<OH at the 4'-position, and the double bond between the 2- and 3-positions were important. The active constituents suppressed tyrosinase, tyrosinase related protein (TRP)-1, and TRP-2 mRNA expression. The suppression was considered as one of the mechanisms of action. Furthermore, the methanolic extract and several constituents, including luteoloside and spiraeoside, showed anti-plasmin activity, which is considered to play a key role in UV-stimulated melanogenesis in human skin.
|
Binding affinity to TTR (unknown origin) by isothermal titration calorimetric analysis
|
Homo sapiens
|
70.0
nM
|
|
Journal : J. Med. Chem.
Title : Enthalpic Forces Correlate with the Selectivity of Transthyretin-Stabilizing Ligands in Human Plasma.
Year : 2015
Volume : 58
Issue : 16
First Page : 6507
Last Page : 6515
Authors : Iakovleva I, Brännström K, Nilsson L, Gharibyan AL, Begum A, Anan I, Walfridsson M, Sauer-Eriksson AE, Olofsson A.
Abstract : The plasma protein transthyretin (TTR) is linked to human amyloidosis. Dissociation of its native tetrameric assembly is a rate-limiting step in the conversion from a native structure into a pathological amyloidogenic fold. Binding of small molecule ligands within the thyroxine binding site of TTR can stabilize the tetrameric integrity and is a potential therapeutic approach. However, through the characterization of nine different tetramer-stabilizing ligands we found that unspecific binding to plasma components might significantly compromise ligand efficacy. Surprisingly the binding strength between a particular ligand and TTR does not correlate well with its selectivity in plasma. However, through analysis of the thermodynamic signature using isothermal titration calorimetry we discovered a better correlation between selectivity and the enthalpic component of the interaction. This is of specific interest in the quest for more efficient TTR stabilizers, but a high selectivity is an almost universally desired feature within drug design and the finding might have wide-ranging implications for drug design.
|
Inhibition of xanthine oxidase (unknown origin) using xanthine as substrate at 33 to 100 umol/L after 10 mins by HPLC method relative to control
|
Homo sapiens
|
50.0
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : An oxidative coupling product of luteolin with cysteine ester and its enhanced inhibitory activity for xanthine oxidase.
Year : 2015
Volume : 25
Issue : 16
First Page : 3117
Last Page : 3119
Authors : Masuda T, Nojima S, Miura Y, Honda S, Masuda A.
Abstract : Oxidative coupling reactions of several flavonoids with a cysteine ester (a radicalic and nucleophilic biochemical) were carried out and the abilities of the coupling products against xanthine oxidase (XO) were screened. One of the products, derived from luteolin, showed a notable inhibitory effect. A potent XO inhibitory compound was isolated from the complex mixture of the product of the coupling of luteolin and cysteine ethyl ester, and its structure was determined by NMR and MS analysis. The compound has a unique 1,4-thiazine ring unit on the luteolin B-ring and is inhibited XO 4.5 times more strongly than it did luteolin.
|
Anti-platelet activity in rat platelet rich plasma assessed as inhibition of ADP and calcium-induced platelet aggregation at 100 uM pre-incubated at 37 degC for 10 mins and measured 30 mins after ADP and calcium addition
|
Rattus norvegicus
|
26.55
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Potential therapeutic agents for circulatory diseases from Bauhinia glauca Benth.subsp. pernervosa. (Da Ye Guan Men).
Year : 2015
Volume : 25
Issue : 16
First Page : 3217
Last Page : 3220
Authors : Tang Y, Ling J, Zhang P, Zhang X, Zhang N, Wang W, Li J, Li N.
Abstract : Because of platelets as critical factor in the formation of pathogenic thrombi, anti-platelet activities have been selected as therapeutic target for various circulatory diseases. In order to find potential therapeutic agents, bioassay-directed separation of Bauhinia glauca Benth.subsp. pernervosa. (called Da Ye Guan Men as a traditional Chinese medicine) was performed to get 29 main components (compounds 1-29) from the bioactive part of this herbal. It was the first time to focus on the composition with anti-platelet aggregation activities for this traditional Chinese medicine. The constituents, characterized from the effective extract, were established on the basis of extensive spectral data analysis. Then their anti-platelet aggregation effects were evaluated systematically. On the basis of the chemical profile and biological assay, it was suggested that the flavonoid composition (5 and 18) should be responsible for the anti-platelet aggregation of the herbal because of their significant activities. The primary structure and activity relationship was also discussed briefly.
|
Inhibition of human recombinant carbonic anhydrase 7 preincubated for 15 mins at room temperature/6 hrs at 4 deg C by stopped-flow CO2 hydration assay
|
Homo sapiens
|
4.7
nM
|
|
Journal : Bioorg. Med. Chem.
Title : New natural product carbonic anhydrase inhibitors incorporating phenol moieties.
Year : 2015
Volume : 23
Issue : 22
First Page : 7219
Last Page : 7225
Authors : Karioti A, Ceruso M, Carta F, Bilia AR, Supuran CT.
Abstract : Carbonic anhydrases (CAs, EC 4.2.1.1) catalyze the fundamental reaction of CO2 hydration in all living organisms, being actively involved in the regulation of a plethora of patho/physiological conditions. They represent a typical example of enzyme convergent evolution, as six genetically unrelated families of such enzymes were described so far. The need to find selective CA inhibitors (CAIs) triggered the investigation of natural product libraries, which proved to be a valid source of agents with such an activity, as demonstrated for the phenols, polyamines and coumarins. Herein we report an in vitro inhibition study of human (h) CA isoforms hCAs I, II, IV, VII and XII with a panel of natural polyphenols including flavones, flavonols, flavanones, flavanols, isoflavones and depsides, some of which extracted from Quercus ilex and Salvia miltiorrhiza. Several of the investigated derivatives showed interesting inhibition activity and selectivities for inhibiting some important isoforms over the off-target ones hCA I and II.
|
Inhibition of human recombinant carbonic anhydrase 12 preincubated for 15 mins at room temperature/6 hrs at 4 deg C by stopped-flow CO2 hydration assay
|
Homo sapiens
|
60.3
nM
|
|
Journal : Bioorg. Med. Chem.
Title : New natural product carbonic anhydrase inhibitors incorporating phenol moieties.
Year : 2015
Volume : 23
Issue : 22
First Page : 7219
Last Page : 7225
Authors : Karioti A, Ceruso M, Carta F, Bilia AR, Supuran CT.
Abstract : Carbonic anhydrases (CAs, EC 4.2.1.1) catalyze the fundamental reaction of CO2 hydration in all living organisms, being actively involved in the regulation of a plethora of patho/physiological conditions. They represent a typical example of enzyme convergent evolution, as six genetically unrelated families of such enzymes were described so far. The need to find selective CA inhibitors (CAIs) triggered the investigation of natural product libraries, which proved to be a valid source of agents with such an activity, as demonstrated for the phenols, polyamines and coumarins. Herein we report an in vitro inhibition study of human (h) CA isoforms hCAs I, II, IV, VII and XII with a panel of natural polyphenols including flavones, flavonols, flavanones, flavanols, isoflavones and depsides, some of which extracted from Quercus ilex and Salvia miltiorrhiza. Several of the investigated derivatives showed interesting inhibition activity and selectivities for inhibiting some important isoforms over the off-target ones hCA I and II.
|
Inhibition of human recombinant carbonic anhydrase 4
|
Homo sapiens
|
293.0
nM
|
|
Journal : Bioorg. Med. Chem.
Title : New natural product carbonic anhydrase inhibitors incorporating phenol moieties.
Year : 2015
Volume : 23
Issue : 22
First Page : 7219
Last Page : 7225
Authors : Karioti A, Ceruso M, Carta F, Bilia AR, Supuran CT.
Abstract : Carbonic anhydrases (CAs, EC 4.2.1.1) catalyze the fundamental reaction of CO2 hydration in all living organisms, being actively involved in the regulation of a plethora of patho/physiological conditions. They represent a typical example of enzyme convergent evolution, as six genetically unrelated families of such enzymes were described so far. The need to find selective CA inhibitors (CAIs) triggered the investigation of natural product libraries, which proved to be a valid source of agents with such an activity, as demonstrated for the phenols, polyamines and coumarins. Herein we report an in vitro inhibition study of human (h) CA isoforms hCAs I, II, IV, VII and XII with a panel of natural polyphenols including flavones, flavonols, flavanones, flavanols, isoflavones and depsides, some of which extracted from Quercus ilex and Salvia miltiorrhiza. Several of the investigated derivatives showed interesting inhibition activity and selectivities for inhibiting some important isoforms over the off-target ones hCA I and II.
|
Inhibition of recombinant human AKR1B10 expressed in human HCT116 cells assessed as reduction in daunorubicinol production using daunorubicin as substrate at 20 uM incubated for 4 to 8 hrs by UHPLC based transient transfection assay
|
Homo sapiens
|
33.0
%
|
|
Journal : J. Nat. Prod.
Title : Flavones Inhibit the Activity of AKR1B10, a Promising Therapeutic Target for Cancer Treatment.
Year : 2015
Volume : 78
Issue : 11
First Page : 2666
Last Page : 2674
Authors : Zemanova L, Hofman J, Novotna E, Musilek K, Lundova T, Havrankova J, Hostalkova A, Chlebek J, Cahlikova L, Wsol V.
Abstract : AKR1B10 is an NADPH-dependent reductase that plays an important function in several physiological reactions such as the conversion of retinal to retinol, reduction of isoprenyl aldehydes, and biotransformation of procarcinogens and drugs. A growing body of evidence points to the important role of the enzyme in the development of several types of cancer (e.g., breast, hepatocellular), in which it is highly overexpressed. AKR1B10 is regarded as a therapeutic target for the treatment of these diseases, and potent and specific inhibitors may be promising therapeutic agents. Several inhibitors of AKR1B10 have been described, but the area of natural plant products has been investigated sparingly. In the present study almost 40 diverse phenolic compounds and alkaloids were examined for their ability to inhibit the recombinant AKR1B10 enzyme. The most potent inhibitors-apigenin, luteolin, and 7-hydroxyflavone-were further characterized in terms of IC50, selectivity, and mode of action. Molecular docking studies were also conducted, which identified putative binding residues important for the interaction. In addition, cellular studies demonstrated a significant inhibition of the AKR1B10-mediated reduction of daunorubicin in intact cells by these inhibitors without a considerable cytotoxic effect. Although these compounds are moderately potent and selective inhibitors of AKR1B10, they constitute a new structural type of AKR1B10 inhibitor and may serve as a template for the development of better inhibitors.
|
Antitrypanosomal activity against Trypanosoma brucei rhodesiense STIB 900 after 72 hrs by alamar blue staining based fluorescence analysis
|
Trypanosoma brucei rhodesiense
|
3.7
ug.mL-1
|
|
Journal : MedChemComm
Title : Focus on PAINS: false friends in the quest for selective anti-protozoal lead structures from Nature?
Year : 2016
Volume : 7
Issue : 2
First Page : 214
Last Page : 223
Authors : Glaser J, Holzgrabe U
|
Cytotoxicity against rat L6 cells after 72 hrs by alamar blue staining based fluorescence analysis
|
Rattus norvegicus
|
9.4
ug.mL-1
|
|
Journal : MedChemComm
Title : Focus on PAINS: false friends in the quest for selective anti-protozoal lead structures from Nature?
Year : 2016
Volume : 7
Issue : 2
First Page : 214
Last Page : 223
Authors : Glaser J, Holzgrabe U
|
Antileishmanial activity against Leishmania donovani MHOM/ET/67/L82 after 72 hrs by Alamar blue dye based fluorescence analysis
|
Leishmania donovani
|
0.8
ug.mL-1
|
|
Journal : MedChemComm
Title : Focus on PAINS: false friends in the quest for selective anti-protozoal lead structures from Nature?
Year : 2016
Volume : 7
Issue : 2
First Page : 214
Last Page : 223
Authors : Glaser J, Holzgrabe U
|
Antitrypanosomal activity against trypomastigote forms of Trypanosoma cruzi Tulahuen C2C4 infected in rat L6 cells after 96 hrs by photometric method
|
Trypanosoma cruzi
|
21.4
ug.mL-1
|
|
Journal : MedChemComm
Title : Focus on PAINS: false friends in the quest for selective anti-protozoal lead structures from Nature?
Year : 2016
Volume : 7
Issue : 2
First Page : 214
Last Page : 223
Authors : Glaser J, Holzgrabe U
|
Inhibition of Bcl-2 (unknown origin) using FAM-Bid peptide as substrate at 50 uM by fluorescence polarization-based assay
|
Homo sapiens
|
46.0
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Structural modification of luteolin from Flos Chrysanthemi leads to increased tumor cell growth inhibitory activity.
Year : 2016
Volume : 26
Issue : 15
First Page : 3464
Last Page : 3467
Authors : Yang C, Chen H, Lu S, Zhang M, Tian W, Wang M, Zhang L, Song Y, Shen A, Zhou Y, Zhu J, Zheng C.
Abstract : The luteolin from Flos Chrysanthemi was found to directly bind to the Bcl-2 protein and inhibit the tumor cell growth in our previous study. However, it has been shown to possess wide and week biological activities. In this study, a series of derivatives of luteolin were designed and synthesized, and their tumor cell growth inhibitory activities were evaluated against human leukemia cell line HL-60. The results showed that compounds 1B-2, 2A-3, and 2B-5, with hydrophobic substituted benzyl groups introduced to B ring and hydrogen or methyl introduced to 7-OH group of luteolin, exhibited the strongest inhibitory activity with the IC50 lower than 10μM, which were significantly more potent than luteolin. The studies presented here offer a good example for modifications of flavones to improve their tumor cell growth inhibitory activities.
|
Inhibition of Bcl-XL (unknown origin) using FAM-Bid peptide as substrate at 50 uM by fluorescence polarization-based assay
|
Homo sapiens
|
49.0
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Structural modification of luteolin from Flos Chrysanthemi leads to increased tumor cell growth inhibitory activity.
Year : 2016
Volume : 26
Issue : 15
First Page : 3464
Last Page : 3467
Authors : Yang C, Chen H, Lu S, Zhang M, Tian W, Wang M, Zhang L, Song Y, Shen A, Zhou Y, Zhu J, Zheng C.
Abstract : The luteolin from Flos Chrysanthemi was found to directly bind to the Bcl-2 protein and inhibit the tumor cell growth in our previous study. However, it has been shown to possess wide and week biological activities. In this study, a series of derivatives of luteolin were designed and synthesized, and their tumor cell growth inhibitory activities were evaluated against human leukemia cell line HL-60. The results showed that compounds 1B-2, 2A-3, and 2B-5, with hydrophobic substituted benzyl groups introduced to B ring and hydrogen or methyl introduced to 7-OH group of luteolin, exhibited the strongest inhibitory activity with the IC50 lower than 10μM, which were significantly more potent than luteolin. The studies presented here offer a good example for modifications of flavones to improve their tumor cell growth inhibitory activities.
|
Inhibition of sucrose loaded POPC/POPE/POPS/PtdIns(3,4,5)P3 (59:20:20:1) liposome binding to eGFP-fused PDK1 PH domain (unknown origin) expressed in Escherichia coli BL21 at 20 uM after 10 mins by fluorescence spectrophotometry based pull down assay relative to control
|
Homo sapiens
|
31.12
%
|
|
Journal : Bioorg Med Chem Lett
Title : Inhibitory potential of flavonoids on PtdIns(3,4,5)P3 binding with the phosphoinositide-dependent kinase 1 pleckstrin homology domain.
Year : 2017
Volume : 27
Issue : 3
First Page : 420
Last Page : 426
Authors : Kang Y, Kim BG, Kim S, Lee Y, Yoon Y.
Abstract : Many membrane-associated proteins are involved in various signaling pathways, including the phosphoinositide 3-kinase (PI3K) pathway, which has key roles in diverse cellular processes. Disruption of the activities of these proteins is involved in the development of disease in humans, making these proteins promising targets for drug development. In most cases, the catalytic domain is targeted; however, it is also possible to target membrane associations in order to regulate protein activity. In this study, we established a novel method to study protein-lipid interactions and screened for flavonoid-derived antagonists of PtdIns(3,4,5)P3 binding with the phosphoinositide-dependent kinase 1 (PDK1) pleckstrin homology (PH) domain. Using an enhanced green fluorescent protein (eGFP)-tagged PDK1 PH domain and 50% sucrose-loaded liposomes, the protein-lipid interaction could be efficiently evaluated using liposome pull-down assays coupled with fluorescence spectrophotometry, and a total of 32 flavonoids were screened as antagonists for PtdIns(3,4,5)P3 binding with the PDK1 PH domain. From this analysis, we found that two adjunct hydroxyl groups in the C ring were responsible for the inhibitory effects of the flavonoids. Because the flavonoids shared structural similarities, the results were then subjected to quantitative structure-activity relationship (QSAR) analysis. The results were then further confirmed by in silico docking experiments. Taken together, our strategy presented herein to screen antagonists targeting lipid-protein interactions could be an alternative method for identification and characterization of drug candidates.
|
Antiinflammatory activity in mouse RAW264.7 cells assessed as inhibition of LPS-stimulated NO production at 5 uM by ELISA relative to control
|
Mus musculus
|
19.5
%
|
|
Journal : Bioorg Med Chem Lett
Title : Identification and structure activity relationship of novel flavone derivatives that inhibit the production of nitric oxide and PGE2 in LPS-induced RAW 264.7 cells.
Year : 2017
Volume : 27
Issue : 11
First Page : 2613
Last Page : 2616
Authors : An JY, Lee HH, Shin JS, Yoo HS, Park JS, Son SH, Kim SW, Yu J, Lee J, Lee KT, Kim NJ.
Abstract : In an effort to identify novel anti-inflammatory compounds, a series of flavone derivatives were synthesized and biologically evaluated for their inhibitory effects on the production of nitric oxide (NO) and prostaglandin E2 (PGE2), representative pro-inflammatory mediators, in LPS-induced RAW 264.7 cells. Their structure-activity relationship was also investigated. In particular, we found that compound 3g displayed more potent inhibitory activities on PGE2 production, similar inhibitory activities on NO production and less weak cytotoxicity than luteolin, a natural flavone known as a potent anti-inflammatory agent.
|
Inhibition of recombinant human CYP1B1 expressed in supersomes using ethoxyresorufin as substrate preincubated for 5 mins followed by substrate addition in presence of NADPH by fluorimetric analysis
|
Homo sapiens
|
360.0
nM
|
|
Journal : Eur J Med Chem
Title : Inhibitors of cytochrome P450 (CYP) 1B1.
Year : 2017
Volume : 135
First Page : 296
Last Page : 306
Authors : Dutour R, Poirier D.
Abstract : Human cytochrome P450 1B1 (CYP1B1) is involved in the metabolism of various drugs. This enzyme catalyzes the hydroxylation of aryl compounds, thus generating more polar metabolites that can be easily excreted. CYP1B1 is also known for its ability to activate procarcinogens into carcinogens. For example, it can hydroxylate 17β-estradiol (E2) into 4-hydroxy-E2, which can promote tumorigenesis as a potent estrogen, or after being transformed into E2-3,4-quinone. Since elevated expression levels of CYP1B1 have been reported in various cancers, but not in normal tissues, this enzyme represents an interesting therapeutic target. This review put emphasis on different families of inhibitors, especially those reported since 2003.
|
Inhibition of HFIP-pretreated amyloid beta (1 to 42) (unknown origin) self-induced aggregation at 20 uM incubated for 24 hrs under dark condition by thioflavin-T based fluorometric assay relative to control
|
Homo sapiens
|
86.5
%
|
|
Journal : Bioorg Med Chem Lett
Title : Flavonoids and their derivatives with β-amyloid aggregation inhibitory activity from the leaves and twigs of Pithecellobium clypearia Benth.
Year : 2017
Volume : 27
Issue : 21
First Page : 4823
Last Page : 4827
Authors : Wang YX, Ren Q, Yan ZY, Wang W, Zhao L, Bai M, Wang XB, Huang XX, Song SJ.
Abstract : To explore potential compounds with marked effect on Alzheimer's disease (AD) in Pithecellobium clypearia Benth., nineteen compounds (1-19) were obtained, including two new flavonoid derivatives, named pithecellobiumol A (1) and pithecellobiumol B (2) and 17 flavonoids (3-19). Their structures were elucidated based on 1D and 2D-NMR spectra as well as HR-ESI-MS data. The absolute configurations of new compounds were assigned by comparing their experimental specific rotation or ECD curves with the calculated data. The inhibitory activity on Aβ aggregation was screened by ThT assay, and compounds 7 (70.7%), 9 (86.5%), 10 (88.4%), 15 (86.1%) and 16 (87.7%) showed outstanding inhibition rate at 20μM compared to the positive control, curcumin (65.64%). In addition, docking study was performed to initially examine possible molecular mechanisms. Considering the important role of oxidative stress in AD, all the isolated compounds were tested for their H2O2-induced damage in human neuronblastoma SH-SY5Y cells. Among them, compound 16 (91.0%) was the most potent candidate in the treatment of AD.
|
Inhibition of Saccharomyces cerevisiae alpha-glucosidase using p-nitro-phenyl-alpha-D-glucopyranoside as substrate at 200 uM preincubated with enzyme followed by substrate addition measured after 10 mins for every 2.5 to 5 mins relative to control
|
Saccharomyces cerevisiae
|
99.6
%
|
|
Journal : Bioorg Med Chem Lett
Title : Chemical constituents from Taraxacum officinale and their α-glucosidase inhibitory activities.
Year : 2018
Volume : 28
Issue : 3
First Page : 476
Last Page : 481
Authors : Choi J, Yoon KD, Kim J.
Abstract : Three novel butyrolactones (1-3) and butanoates (4-6), namely taraxiroside A-F, were isolated from Taraxacum officinale along with twenty-two known compounds (7-28). Their chemical structures were elucidated by interpretation of spectroscopic data and comparison with those of literatures. All isolates were evaluated for their α-glucosidase inhibitory activities. Novel compounds 1-6 (IC50 145.3-181.3 μM) showed inhibitory activities similar to that of acarbose (IC50 179.9 μM). Compound 7 and 12 were the most potent inhibitor with IC50 values of 61.2 and 39.8 μM respectively. Compounds 2 and 12 showed as mixed-type inhibition, whereas compound 7 and acarbose showed competitive inhibition.
|
Inhibition of DPP4 (unknown origin) using Gly-Pro-AMC as substrate preincubated for 4 secs followed by substrate addition and measured after 30 mins by luminescence assay
|
Homo sapiens
|
120.0
nM
|
|
Journal : Eur J Med Chem
Title : Recent progress of the development of dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes mellitus.
Year : 2018
Volume : 151
First Page : 145
Last Page : 157
Authors : Li N, Wang LJ, Jiang B, Li XQ, Guo CL, Guo SJ, Shi DY.
Abstract : Diabetes is a fast growing chronic metabolic disorder around the world. Dipeptidyl peptidase-4 (DPP-4) is a new promising target during type 2 diabetes glycemic control. Thus, a number of potent DPP-4 inhibitors were developed and play a rapidly evolving role in the management of type 2 diabetes in recent years. This article reviews the development of synthetic and natural DPP-4 inhibitors from 2012 to 2017 and provides their physico-chemical properties, biological activities against DPP-4 and selectivity over dipeptidyl peptidase-8/9. Moreover, the glucose-lowering mechanisms and the active site of DPP-4 are also discussed. We also discuss strategies and structure-activity relationships for identifying potent DPP-4 inhibitors, which will provide useful information for developing potent DPP-4 drugs as type 2 diabtes treatments.
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging
|
Homo sapiens
|
1.01
%
|
|
Title : Identification of inhibitors of SARS-CoV-2 in-vitro cellular toxicity in human (Caco-2) cells using a large scale drug repurposing collection
Year : 2020
Authors : Bernhard Ellinger, Denisa Bojkova, Andrea Zaliani, Jindrich Cinatl, Carsten Claussen, Sandra Westhaus, Jeanette Reinshagen, Maria Kuzikov, Markus Wolf, Gerd Geisslinger, Philip Gribbon, Sandra Ciesek
Abstract : To identify possible candidates for progression towards clinical studies against SARS-CoV-2, we screened a well-defined collection of 5632 compounds including 3488 compounds which have undergone clinical investigations (marketed drugs, phases 1 -3, and withdrawn) across 600 indications. Compounds were screened for their inhibition of viral induced cytotoxicity using the human epithelial colorectal adenocarcinoma cell line Caco-2 and a SARS-CoV-2 isolate. The primary screen of 5632 compounds gave 271 hits. A total of 64 compounds with IC50 <20 µM were identified, including 19 compounds with IC50 < 1 µM. Of this confirmed hit population, 90% have not yet been previously reported as active against SARS-CoV-2 in-vitro cell assays. Some 37 of the actives are launched drugs, 19 are in phases 1-3 and 10 pre-clinical. Several inhibitors were associated with modulation of host pathways including kinase signaling P53 activation, ubiquitin pathways and PDE activity modulation, with long chain acyl transferases were effective viral inhibitors.
|
Inhibition of human recombinant full length PTP1B expressed in Escherichia coli cells at 1 uM using pNPP as substrate preincubated with enzyme for 5 mins followed by incubation with substrate for 10 mins by spectrophotometry analysis relative to control
|
Homo sapiens
|
19.8
%
|
|
Journal : Eur J Med Chem
Title : New insights into the biological activities of Chrysanthemum morifolium: Natural flavonoids alleviate diabetes by targeting α-glucosidase and the PTP-1B signaling pathway.
Year : 2019
Volume : 178
First Page : 108
Last Page : 115
Authors : Chen M, Wang K, Zhang Y, Zhang M, Ma Y, Sun H, Jin Z, Zheng H, Jiang H, Yu P, Zhang Y, Sun H.
Abstract : As dual regulators, the PTP-1B signaling pathway and α-glucosidase slow glucose release and increase the degree of insulin sensitivity, representing a promising therapeutic target for type 2 diabetes. In this study, we systematically examined the in vivo and in vitro anti-diabetic activities of natural flavonoids 1-6 from Chrysanthemum morifolium. Flavonoids 1-6 increased glucose consumption-promoting activity and the phosphorylation of GSK-3β and Akt, and decreased PTP-1B protein level along with slightly inhibitory activity of the PTP-1B enzyme. Moreover, flavonoids 1-2 treatment induced insulin secretion in INS-1 cells. Besides, in vivo study revealed that flavonoids 2 and 5 demonstrated potent anti-hyperglycemic and anti-hyperlipidemic activity, and improved maltose and glucose tolerance. Although flavonoid 2 exhibited lower inhibitory activity against α-glucosidase in vitro, it could deglycosylated in vivo to diosmetin to function as an α-glucosidase inhibitor. Taken together, these results led to the identification of the natural flavonoids 1-6 from C. morifolium as dual regulators of α-glucosidase and the PTP-1B signaling pathway, suggesting their potential application as new oral anti-diabetic drugs or functional food ingredients.
|
Inhibition of human recombinant full length PTP1B expressed in Escherichia coli cells at 5 uM using pNPP as substrate preincubated with enzyme for 5 mins followed by incubation with substrate for 10 mins by spectrophotometry analysis relative to control
|
Homo sapiens
|
40.75
%
|
|
Journal : Eur J Med Chem
Title : New insights into the biological activities of Chrysanthemum morifolium: Natural flavonoids alleviate diabetes by targeting α-glucosidase and the PTP-1B signaling pathway.
Year : 2019
Volume : 178
First Page : 108
Last Page : 115
Authors : Chen M, Wang K, Zhang Y, Zhang M, Ma Y, Sun H, Jin Z, Zheng H, Jiang H, Yu P, Zhang Y, Sun H.
Abstract : As dual regulators, the PTP-1B signaling pathway and α-glucosidase slow glucose release and increase the degree of insulin sensitivity, representing a promising therapeutic target for type 2 diabetes. In this study, we systematically examined the in vivo and in vitro anti-diabetic activities of natural flavonoids 1-6 from Chrysanthemum morifolium. Flavonoids 1-6 increased glucose consumption-promoting activity and the phosphorylation of GSK-3β and Akt, and decreased PTP-1B protein level along with slightly inhibitory activity of the PTP-1B enzyme. Moreover, flavonoids 1-2 treatment induced insulin secretion in INS-1 cells. Besides, in vivo study revealed that flavonoids 2 and 5 demonstrated potent anti-hyperglycemic and anti-hyperlipidemic activity, and improved maltose and glucose tolerance. Although flavonoid 2 exhibited lower inhibitory activity against α-glucosidase in vitro, it could deglycosylated in vivo to diosmetin to function as an α-glucosidase inhibitor. Taken together, these results led to the identification of the natural flavonoids 1-6 from C. morifolium as dual regulators of α-glucosidase and the PTP-1B signaling pathway, suggesting their potential application as new oral anti-diabetic drugs or functional food ingredients.
|
Inhibition of human recombinant full length PTP1B expressed in Escherichia coli cells at 10 uM using pNPP as substrate preincubated with enzyme for 5 mins followed by incubation with substrate for 10 mins by spectrophotometry analysis relative to control
|
Homo sapiens
|
39.92
%
|
|
Journal : Eur J Med Chem
Title : New insights into the biological activities of Chrysanthemum morifolium: Natural flavonoids alleviate diabetes by targeting α-glucosidase and the PTP-1B signaling pathway.
Year : 2019
Volume : 178
First Page : 108
Last Page : 115
Authors : Chen M, Wang K, Zhang Y, Zhang M, Ma Y, Sun H, Jin Z, Zheng H, Jiang H, Yu P, Zhang Y, Sun H.
Abstract : As dual regulators, the PTP-1B signaling pathway and α-glucosidase slow glucose release and increase the degree of insulin sensitivity, representing a promising therapeutic target for type 2 diabetes. In this study, we systematically examined the in vivo and in vitro anti-diabetic activities of natural flavonoids 1-6 from Chrysanthemum morifolium. Flavonoids 1-6 increased glucose consumption-promoting activity and the phosphorylation of GSK-3β and Akt, and decreased PTP-1B protein level along with slightly inhibitory activity of the PTP-1B enzyme. Moreover, flavonoids 1-2 treatment induced insulin secretion in INS-1 cells. Besides, in vivo study revealed that flavonoids 2 and 5 demonstrated potent anti-hyperglycemic and anti-hyperlipidemic activity, and improved maltose and glucose tolerance. Although flavonoid 2 exhibited lower inhibitory activity against α-glucosidase in vitro, it could deglycosylated in vivo to diosmetin to function as an α-glucosidase inhibitor. Taken together, these results led to the identification of the natural flavonoids 1-6 from C. morifolium as dual regulators of α-glucosidase and the PTP-1B signaling pathway, suggesting their potential application as new oral anti-diabetic drugs or functional food ingredients.
|
Inhibition of human recombinant CK2 expressed in Escherichia coli using RRRADDSDDDDD as substrate after 10 mins in presence of [gamma-32P]ATP
|
Homo sapiens
|
500.0
nM
|
|
Journal : Bioorg Med Chem
Title : A review on flavones targeting serine/threonine protein kinases for potential anticancer drugs.
Year : 2019
Volume : 27
Issue : 5
First Page : 677
Last Page : 685
Authors : Zhao L, Yuan X, Wang J, Feng Y, Ji F, Li Z, Bian J.
Abstract : Protein kinases have been important targets for antitumor targets due to their key roles in regulating multiple cell signaling pathways. Numerous compounds containing flavonoid scaffold as an indispensable anchor have been found to be potent inhibitors of protein kinases. Some of these flavonoids have been in clinical research as protein kinases inhibitors. Thus, the present review mainly focuses on the structural requirement for anticancer potential of flavone derivatives targeting several key serine/threonine protein kinases. This information may provide an opportunity to scientists of medicinal chemistry to design multi-functional flavone derivatives for the treatment of cancer.
|
Inhibition of PKC in rat brain homogenate at 50 uM using FKKSFKL-NH2 as substrate preincubated for 10 mins followed by substrate addition and measured after 5 mins in presence of [gamma-32P]ATP by liquid scintillation counting analysis relative to control
|
Rattus norvegicus
|
70.0
%
|
|
Journal : Bioorg Med Chem
Title : A review on flavones targeting serine/threonine protein kinases for potential anticancer drugs.
Year : 2019
Volume : 27
Issue : 5
First Page : 677
Last Page : 685
Authors : Zhao L, Yuan X, Wang J, Feng Y, Ji F, Li Z, Bian J.
Abstract : Protein kinases have been important targets for antitumor targets due to their key roles in regulating multiple cell signaling pathways. Numerous compounds containing flavonoid scaffold as an indispensable anchor have been found to be potent inhibitors of protein kinases. Some of these flavonoids have been in clinical research as protein kinases inhibitors. Thus, the present review mainly focuses on the structural requirement for anticancer potential of flavone derivatives targeting several key serine/threonine protein kinases. This information may provide an opportunity to scientists of medicinal chemistry to design multi-functional flavone derivatives for the treatment of cancer.
|
Inhibition of F1F0-ATP synthase in Escherichia coli after 60 mins relative to control
|
Escherichia coli
|
0.0
%
|
|
Journal : Eur J Med Chem
Title : Recent advancements in mechanistic studies and structure activity relationship of FoF1 ATP synthase inhibitor as antimicrobial agent.
Year : 2019
Volume : 182
First Page : 111644
Last Page : 111644
Authors : Narang R, Kumar R, Kalra S, Nayak SK, Khatik GL, Kumar GN, Sudhakar K, Singh SK.
Abstract : The emergence of drug resistance in infectious microbial strains can be overcome by development of novel drug molecules against unexploited microbial target. The success of Bedaquiline in recent years, as FoF1 ATP synthase inhibitor against XDR and MDR mycobacterium strains, has resulted in further exploration to identify more potent and safe drug molecules against resistant strains. FoF1 ATP synthase is the main energy production enzyme in almost all eukaryotes and prokaryotes. Development of bacterial ATP synthase inhibitors is a safe approach, without causing harm to mammalian cells due to structural difference between bacterial and mammalian ATP synthase target sites. This review emphasizes on providing the structural insights for FoF1 ATP synthase of different prokaryotes and will help in the design of new potent antimicrobial agents with better efficacy. Further, applications of synthetic and natural active antimicrobial ATP synthase inhibitors, reported by different research groups are summarized. Their SAR and mode of actions are also analysed.
|
Inhibition of T0901317-induced LXR-alpha/beta transactivation in mouse RAW264.7 cells assessed as reduction in ABCA1 mRNA expression at 25 uM after 3 hrs by RT-PCR method relative to control
|
Mus musculus
|
41.0
%
|
|
Journal : J Nat Prod
Title : The Flavone Luteolin Inhibits Liver X Receptor Activation.
Year : 2016
Volume : 79
Issue : 5
First Page : 1423
Last Page : 1428
Authors : Francisco V, Figueirinha A, Costa G, Liberal J, Ferreira I, Ferreira I, Lopes MC, García-Rodríguez C, Cruz MT, Batista MT.
Abstract : Luteolin is a dietary flavonoid with medicinal properties including antioxidant, antimicrobial, anticancer, antiallergic, and anti-inflammatory. However, the effect of luteolin on liver X receptors (LXRs), oxysterol sensors that regulate cholesterol homeostasis, lipogenesis, and inflammation, has yet to be studied. To unveil the potential of luteolin as an LXRα/β modulator, we investigated by real-time RT-PCR the expression of LXR-target genes, namely, sterol regulatory element binding protein 1c (SREBP-1c) in hepatocytes and ATP-binding cassette transporter (ABC)A1 in macrophages. The lipid content of hepatocytes was evaluated by Oil Red staining. The results demonstrated, for the first time, that luteolin abrogated the LXRα/β agonist-induced LXRα/β transcriptional activity and, consequently, inhibited SREBP-1c expression, lipid accumulation, and ABCA1 expression. Therefore, luteolin could abrogate hypertriglyceridemia associated with LXR activation, thus presenting putative therapeutic effects in diseases associated with deregulated lipid metabolism, such as hepatic steatosis, cardiovascular diseases, and diabetes.
|
Inhibition of T0901317-induced LXR-alpha/beta transactivation in mouse RAW264.7 cells assessed as reduction in ABCA1 mRNA expression at 50 uM after 3 hrs by RT-PCR method relative to control
|
Mus musculus
|
64.0
%
|
|
Journal : J Nat Prod
Title : The Flavone Luteolin Inhibits Liver X Receptor Activation.
Year : 2016
Volume : 79
Issue : 5
First Page : 1423
Last Page : 1428
Authors : Francisco V, Figueirinha A, Costa G, Liberal J, Ferreira I, Ferreira I, Lopes MC, García-Rodríguez C, Cruz MT, Batista MT.
Abstract : Luteolin is a dietary flavonoid with medicinal properties including antioxidant, antimicrobial, anticancer, antiallergic, and anti-inflammatory. However, the effect of luteolin on liver X receptors (LXRs), oxysterol sensors that regulate cholesterol homeostasis, lipogenesis, and inflammation, has yet to be studied. To unveil the potential of luteolin as an LXRα/β modulator, we investigated by real-time RT-PCR the expression of LXR-target genes, namely, sterol regulatory element binding protein 1c (SREBP-1c) in hepatocytes and ATP-binding cassette transporter (ABC)A1 in macrophages. The lipid content of hepatocytes was evaluated by Oil Red staining. The results demonstrated, for the first time, that luteolin abrogated the LXRα/β agonist-induced LXRα/β transcriptional activity and, consequently, inhibited SREBP-1c expression, lipid accumulation, and ABCA1 expression. Therefore, luteolin could abrogate hypertriglyceridemia associated with LXR activation, thus presenting putative therapeutic effects in diseases associated with deregulated lipid metabolism, such as hepatic steatosis, cardiovascular diseases, and diabetes.
|
Antihyperlipidemic activity in ethanol-induced steatosis C57BL/6 mouse model assessed as inhibition of serum triacylglycerol level at 50 mg/kg, po administered daily through oral gavage for 2 weeks by colorimetric method relative to control
|
Mus musculus
|
22.0
%
|
|
Journal : J Nat Prod
Title : The Flavone Luteolin Inhibits Liver X Receptor Activation.
Year : 2016
Volume : 79
Issue : 5
First Page : 1423
Last Page : 1428
Authors : Francisco V, Figueirinha A, Costa G, Liberal J, Ferreira I, Ferreira I, Lopes MC, García-Rodríguez C, Cruz MT, Batista MT.
Abstract : Luteolin is a dietary flavonoid with medicinal properties including antioxidant, antimicrobial, anticancer, antiallergic, and anti-inflammatory. However, the effect of luteolin on liver X receptors (LXRs), oxysterol sensors that regulate cholesterol homeostasis, lipogenesis, and inflammation, has yet to be studied. To unveil the potential of luteolin as an LXRα/β modulator, we investigated by real-time RT-PCR the expression of LXR-target genes, namely, sterol regulatory element binding protein 1c (SREBP-1c) in hepatocytes and ATP-binding cassette transporter (ABC)A1 in macrophages. The lipid content of hepatocytes was evaluated by Oil Red staining. The results demonstrated, for the first time, that luteolin abrogated the LXRα/β agonist-induced LXRα/β transcriptional activity and, consequently, inhibited SREBP-1c expression, lipid accumulation, and ABCA1 expression. Therefore, luteolin could abrogate hypertriglyceridemia associated with LXR activation, thus presenting putative therapeutic effects in diseases associated with deregulated lipid metabolism, such as hepatic steatosis, cardiovascular diseases, and diabetes.
|
Antihyperlipidemic activity in ethanol-induced steatosis C57BL/6 mouse model assessed as inhibition of serum LDL cholesterol level at 50 mg/kg, po administered daily through oral gavage for 2 weeks by colorimetric method relative to control
|
Mus musculus
|
52.0
%
|
|
Journal : J Nat Prod
Title : The Flavone Luteolin Inhibits Liver X Receptor Activation.
Year : 2016
Volume : 79
Issue : 5
First Page : 1423
Last Page : 1428
Authors : Francisco V, Figueirinha A, Costa G, Liberal J, Ferreira I, Ferreira I, Lopes MC, García-Rodríguez C, Cruz MT, Batista MT.
Abstract : Luteolin is a dietary flavonoid with medicinal properties including antioxidant, antimicrobial, anticancer, antiallergic, and anti-inflammatory. However, the effect of luteolin on liver X receptors (LXRs), oxysterol sensors that regulate cholesterol homeostasis, lipogenesis, and inflammation, has yet to be studied. To unveil the potential of luteolin as an LXRα/β modulator, we investigated by real-time RT-PCR the expression of LXR-target genes, namely, sterol regulatory element binding protein 1c (SREBP-1c) in hepatocytes and ATP-binding cassette transporter (ABC)A1 in macrophages. The lipid content of hepatocytes was evaluated by Oil Red staining. The results demonstrated, for the first time, that luteolin abrogated the LXRα/β agonist-induced LXRα/β transcriptional activity and, consequently, inhibited SREBP-1c expression, lipid accumulation, and ABCA1 expression. Therefore, luteolin could abrogate hypertriglyceridemia associated with LXR activation, thus presenting putative therapeutic effects in diseases associated with deregulated lipid metabolism, such as hepatic steatosis, cardiovascular diseases, and diabetes.
|
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate
|
Severe acute respiratory syndrome coronavirus 2
|
-3.027
%
|
|
Title : Identification of inhibitors of SARS-Cov2 M-Pro enzymatic activity using a small molecule repurposing screen
Year : 2020
Authors : Maria Kuzikov, Elisa Costanzi, Jeanette Reinshagen, Francesca Esposito, Laura Vangeel, Markus Wolf, Bernhard Ellinger, Carsten Claussen, Gerd Geisslinger, Angela Corona, Daniela Iaconis, Carmine Talarico, Candida Manelfi, Rolando Cannalire, Giulia Rossetti, Jonas Gossen, Simone Albani, Francesco Musiani, Katja Herzog, Yang Ye, Barbara Giabbai, Nicola Demitri, Dirk Jochmans, Steven De Jonghe, Jasper Rymenants, Vincenzo Summa, Enzo Tramontano, Andrea R. Beccari, Pieter Leyssen, Paola Storici, Johan Neyts, Philip Gribbon, and Andrea Zaliani
Abstract : Compound repurposing is an important strategy being pursued in the identification of effective treatment against the SARS-CoV-2 infection and COVID-19 disease. In this regard, SARS-CoV-2 main protease (M-Pro), also termed 3CL-Pro, is an attractive drug target as it plays a central role in viral replication by processing the viral polyprotein into 11 non-structural proteins. We report the results of a screening campaign involving ca 8.7 K compounds containing marketed drugs, clinical and preclinical candidates, and chemicals regarded as safe in humans. We confirmed previously reported inhibitors of 3CL-Pro, but we have also identified 68 compounds with IC50 lower than 1 uM and 127 compounds with IC50 lower than 5 uM. Profiling showed 67% of confirmed hits were selective (> 5 fold) against other Cys- and Ser- proteases (Chymotrypsin and Cathepsin-L) and MERS 3CL-Pro. Selected compounds were also analysed in their binding characteristics.
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
-0.07
%
|
|
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging
|
Chlorocebus sabaeus
|
-0.07
%
|
|
Title : Cytopathic SARS-Cov2 screening on VERO-E6 cells in a large repurposing effort
Year : 2020
Authors : Andrea Zaliani, Laura Vangeel, Jeanette Reinshagen, Daniela Iaconis, Maria Kuzikov, Oliver Keminer, Markus Wolf, Bernhard Ellinger, Francesca Esposito, Angela Corona, Enzo Tramontano, Candida Manelfi, Katja Herzog, Dirk Jochmans, Steven De Jonghe, Winston Chiu, Thibault Francken, Joost Schepers, Caroline Collard, Kayvan Abbasi, Carsten Claussen , Vincenzo Summa, Andrea R. Beccari, Johan Neyts, Philip Gribbon and Pieter Leyssen
Abstract : Worldwide, there are intensive efforts to identify repurposed drugs as potential therapies against SARS-CoV-2 infection and the associated COVID-19 disease. To date, the anti-inflammatory drug dexamethasone and (to a lesser extent) the RNA-polymerase inhibitor remdesivir have been shown to be effective in reducing mortality and patient time to recovery, respectively, in patients. Here, we report the results of a phenotypic screening campaign within an EU-funded project (H2020-EXSCALATE4COV) aimed at extending the repertoire of anti-COVID therapeutics through repurposing of available compounds and highlighting compounds with new mechanisms of action against viral infection. We screened 8702 molecules from different repurposing libraries, to reveal 110 compounds with an anti-cytopathic IC50 < 20 µM. From this group, 18 with a safety index greater than 2 are also marketed drugs, making them suitable for further study as potential therapies against COVID-19. Our result supports the idea that a systematic approach to repurposing is a valid strategy to accelerate the necessary drug discovery process.
|
In-vivo inhibition of ICR mouse beta-glucuronidase at 20 mg/kg, sc after 10 weeks relative to DMH alone
|
Mus musculus
|
14.9
%
|
|
Journal : Eur J Med Chem
Title : Therapeutic significance of β-glucuronidase activity and its inhibitors: A review.
Year : 2020
Volume : 187
First Page : 111921
Last Page : 111921
Authors : Awolade P, Cele N, Kerru N, Gummidi L, Oluwakemi E, Singh P.
Abstract : The emergence of disease and dearth of effective pharmacological agents on most therapeutic fronts, constitutes a major threat to global public health and man's existence. Consequently, this has created an exigency in the search for new drugs with improved clinical utility or means of potentiating available ones. To this end, accumulating empirical evidence supports molecular target therapy as a plausible egress and, β-glucuronidase (βGLU) - a lysosomal acid hydrolase responsible for the catalytic deconjugation of β-d-glucuronides has emerged as a viable molecular target for several therapeutic applications. The enzyme's activity level in body fluids is also deemed a potential biomarker for the diagnosis of some pathological conditions. Moreover, due to its role in colon carcinogenesis and certain drug-induced dose-limiting toxicities, the development of potent inhibitors of βGLU in human intestinal microbiota has aroused increased attention over the years. Nevertheless, although our literature survey revealed both natural products and synthetic scaffolds as potential inhibitors of the enzyme, only few of these have found clinical utility, albeit with moderate to poor pharmacokinetic profile. Hence, in this review we present a compendium of exploits in the present millennium directed towards the inhibition of βGLU. The aim is to proffer a platform on which new scaffolds can be modelled for improved βGLU inhibitory potency and the development of new therapeutic agents in consequential.
|
In-vivo inhibition of ICR mouse beta-glucuronidase at 60 mg/kg, sc after 10 weeks relative to DMH alone
|
Mus musculus
|
21.3
%
|
|
Journal : Eur J Med Chem
Title : Therapeutic significance of β-glucuronidase activity and its inhibitors: A review.
Year : 2020
Volume : 187
First Page : 111921
Last Page : 111921
Authors : Awolade P, Cele N, Kerru N, Gummidi L, Oluwakemi E, Singh P.
Abstract : The emergence of disease and dearth of effective pharmacological agents on most therapeutic fronts, constitutes a major threat to global public health and man's existence. Consequently, this has created an exigency in the search for new drugs with improved clinical utility or means of potentiating available ones. To this end, accumulating empirical evidence supports molecular target therapy as a plausible egress and, β-glucuronidase (βGLU) - a lysosomal acid hydrolase responsible for the catalytic deconjugation of β-d-glucuronides has emerged as a viable molecular target for several therapeutic applications. The enzyme's activity level in body fluids is also deemed a potential biomarker for the diagnosis of some pathological conditions. Moreover, due to its role in colon carcinogenesis and certain drug-induced dose-limiting toxicities, the development of potent inhibitors of βGLU in human intestinal microbiota has aroused increased attention over the years. Nevertheless, although our literature survey revealed both natural products and synthetic scaffolds as potential inhibitors of the enzyme, only few of these have found clinical utility, albeit with moderate to poor pharmacokinetic profile. Hence, in this review we present a compendium of exploits in the present millennium directed towards the inhibition of βGLU. The aim is to proffer a platform on which new scaffolds can be modelled for improved βGLU inhibitory potency and the development of new therapeutic agents in consequential.
|
Inhibition of human liver FBP1 at 200 uM incubated for 5 mins by fluorescence method relative to control
|
Homo sapiens
|
22.0
%
|
|
Journal : J Nat Prod
Title : Structural Specificity of Flavonoids in the Inhibition of Human Fructose 1,6-Bisphosphatase.
Year : 2020
Volume : 83
Issue : 5
First Page : 1541
Last Page : 1552
Authors : Proença C, Oliveira A, Freitas M, Ribeiro D, Sousa JLC, Ramos MJ, Silva AMS, Fernandes PA, Fernandes E.
Abstract : Liver fructose 1,6-bisphosphatase (FBPase) is a recognized regulatory enzyme of the gluconeogenesis pathway, which has emerged as a valid target to control gluconeogenesis-mediated overproduction of glucose. As such, the management of diabetes with FBPase inhibitors represents a potential alternative for the currently used antidiabetic agents. In this study, the FBPase inhibition of a panel of 55 structurally related flavonoids was tested, through a microanalysis screening system. Then, a subset of seven active inhibitors and their close chemical relatives were further evaluated by molecular dynamics (MD) simulations using a linear interaction energy (LIE) approach. The results obtained showed that D14 (herbacetin) was the most potent inhibitor, suggesting that the presence of -OH groups at the C-3, C-4', C-5, C-7, and C-8 positions, as well as the double bond between C-2 and C-3 and the 4-oxo function at the pyrone ring, are favorable for the intended effect. Furthermore, D14 (herbacetin) is stabilized by a strong interaction with the Glu30 side chain and the Thr24 backbone of FBPase. This is the first investigation studying the in vitro inhibitory effect of a panel of flavonoids against human liver FBPase, thus representing a potentially important step for the search and design of novel inhibitors of this enzyme.
|
Inhibition of N-terminal GST-tagged recombinant human full length MNK2 expressed in baculovirus expression system at 10 uM incubated for 1 hr by Kinase Tracer 236 based LanthaScreen Eu kinase binding assay relative to control
|
Homo sapiens
|
70.0
%
|
|
Journal : J Nat Prod
Title : Biological Evaluation of Selected Flavonoids as Inhibitors of MNKs Targeting Acute Myeloid Leukemia.
Year : 2020
Volume : 83
Issue : 10
First Page : 2967
Last Page : 2975
Authors : Chen LC,Huang HL,HuangFu WC,Yen SC,Ngo ST,Wu YW,Lin TE,Sung TY,Lien ST,Tseng HJ,Pan SL,Huang WJ,Hsu KC
Abstract : Excessive eIF4E phosphorylation by mitogen-activated protein kinase (MAPK)-interacting kinases 1 and 2 (MNK1 and MNK2; collectively, MNKs) has been associated with oncogenesis. The overexpression of eIF4E in acute myeloid leukemia (AML) is related to cancer cell growth and survival. Thus, the inhibition of MNKs and eIF4E phosphorylation are potential therapeutic strategies for AML. Herein, a structure-based virtual screening approach was performed to identify potential MNK inhibitors from natural products. Three flavonoids, apigenin, hispidulin, and luteolin, showed MNK2 inhibitory activity with IC values of 308, 252, and 579 nM, respectively. A structure-activity relationship analysis was performed to disclose the molecular interactions. Furthermore, luteolin exhibited substantial inhibitory efficacy against MNK1 (IC = 179 nM). Experimental results from cellular assays showed that hispidulin and luteolin inhibited the growth of MOLM-13 and MV4-11 AML cells by downregulating eIF4E phosphorylation and arresting the cell cycle at the G0/G1 phase. Therefore, hispidulin and luteolin showed promising results as lead compounds for the potential treatment for AML.
|
Inhibition of N-terminal GST-tagged recombinant human full length MNK2 expressed in baculovirus expression system incubated for 1 hr by Kinase Tracer 236 based LanthaScreen Eu kinase binding assay relative to control
|
Homo sapiens
|
579.0
nM
|
|
Journal : J Nat Prod
Title : Biological Evaluation of Selected Flavonoids as Inhibitors of MNKs Targeting Acute Myeloid Leukemia.
Year : 2020
Volume : 83
Issue : 10
First Page : 2967
Last Page : 2975
Authors : Chen LC,Huang HL,HuangFu WC,Yen SC,Ngo ST,Wu YW,Lin TE,Sung TY,Lien ST,Tseng HJ,Pan SL,Huang WJ,Hsu KC
Abstract : Excessive eIF4E phosphorylation by mitogen-activated protein kinase (MAPK)-interacting kinases 1 and 2 (MNK1 and MNK2; collectively, MNKs) has been associated with oncogenesis. The overexpression of eIF4E in acute myeloid leukemia (AML) is related to cancer cell growth and survival. Thus, the inhibition of MNKs and eIF4E phosphorylation are potential therapeutic strategies for AML. Herein, a structure-based virtual screening approach was performed to identify potential MNK inhibitors from natural products. Three flavonoids, apigenin, hispidulin, and luteolin, showed MNK2 inhibitory activity with IC values of 308, 252, and 579 nM, respectively. A structure-activity relationship analysis was performed to disclose the molecular interactions. Furthermore, luteolin exhibited substantial inhibitory efficacy against MNK1 (IC = 179 nM). Experimental results from cellular assays showed that hispidulin and luteolin inhibited the growth of MOLM-13 and MV4-11 AML cells by downregulating eIF4E phosphorylation and arresting the cell cycle at the G0/G1 phase. Therefore, hispidulin and luteolin showed promising results as lead compounds for the potential treatment for AML.
|
Inhibition of GST-tagged recombinant human full length MNK1 expressed in insect cells at 10 uM relative to control
|
Homo sapiens
|
70.0
%
|
|
Journal : J Nat Prod
Title : Biological Evaluation of Selected Flavonoids as Inhibitors of MNKs Targeting Acute Myeloid Leukemia.
Year : 2020
Volume : 83
Issue : 10
First Page : 2967
Last Page : 2975
Authors : Chen LC,Huang HL,HuangFu WC,Yen SC,Ngo ST,Wu YW,Lin TE,Sung TY,Lien ST,Tseng HJ,Pan SL,Huang WJ,Hsu KC
Abstract : Excessive eIF4E phosphorylation by mitogen-activated protein kinase (MAPK)-interacting kinases 1 and 2 (MNK1 and MNK2; collectively, MNKs) has been associated with oncogenesis. The overexpression of eIF4E in acute myeloid leukemia (AML) is related to cancer cell growth and survival. Thus, the inhibition of MNKs and eIF4E phosphorylation are potential therapeutic strategies for AML. Herein, a structure-based virtual screening approach was performed to identify potential MNK inhibitors from natural products. Three flavonoids, apigenin, hispidulin, and luteolin, showed MNK2 inhibitory activity with IC values of 308, 252, and 579 nM, respectively. A structure-activity relationship analysis was performed to disclose the molecular interactions. Furthermore, luteolin exhibited substantial inhibitory efficacy against MNK1 (IC = 179 nM). Experimental results from cellular assays showed that hispidulin and luteolin inhibited the growth of MOLM-13 and MV4-11 AML cells by downregulating eIF4E phosphorylation and arresting the cell cycle at the G0/G1 phase. Therefore, hispidulin and luteolin showed promising results as lead compounds for the potential treatment for AML.
|
Inhibition of GST-tagged recombinant human full length MNK1 expressed in insect cells
|
Homo sapiens
|
179.0
nM
|
|
Journal : J Nat Prod
Title : Biological Evaluation of Selected Flavonoids as Inhibitors of MNKs Targeting Acute Myeloid Leukemia.
Year : 2020
Volume : 83
Issue : 10
First Page : 2967
Last Page : 2975
Authors : Chen LC,Huang HL,HuangFu WC,Yen SC,Ngo ST,Wu YW,Lin TE,Sung TY,Lien ST,Tseng HJ,Pan SL,Huang WJ,Hsu KC
Abstract : Excessive eIF4E phosphorylation by mitogen-activated protein kinase (MAPK)-interacting kinases 1 and 2 (MNK1 and MNK2; collectively, MNKs) has been associated with oncogenesis. The overexpression of eIF4E in acute myeloid leukemia (AML) is related to cancer cell growth and survival. Thus, the inhibition of MNKs and eIF4E phosphorylation are potential therapeutic strategies for AML. Herein, a structure-based virtual screening approach was performed to identify potential MNK inhibitors from natural products. Three flavonoids, apigenin, hispidulin, and luteolin, showed MNK2 inhibitory activity with IC values of 308, 252, and 579 nM, respectively. A structure-activity relationship analysis was performed to disclose the molecular interactions. Furthermore, luteolin exhibited substantial inhibitory efficacy against MNK1 (IC = 179 nM). Experimental results from cellular assays showed that hispidulin and luteolin inhibited the growth of MOLM-13 and MV4-11 AML cells by downregulating eIF4E phosphorylation and arresting the cell cycle at the G0/G1 phase. Therefore, hispidulin and luteolin showed promising results as lead compounds for the potential treatment for AML.
|
Inhibition of MNK1/MNK2 in human MV4-11 cells assessed as reduction in eIF4E phosphorylation reduction in eIF4E phosphorylation at 10 uM after 24 to 48 hrs by Western blot analysis
|
Homo sapiens
|
100.0
%
|
|
Journal : J Nat Prod
Title : Biological Evaluation of Selected Flavonoids as Inhibitors of MNKs Targeting Acute Myeloid Leukemia.
Year : 2020
Volume : 83
Issue : 10
First Page : 2967
Last Page : 2975
Authors : Chen LC,Huang HL,HuangFu WC,Yen SC,Ngo ST,Wu YW,Lin TE,Sung TY,Lien ST,Tseng HJ,Pan SL,Huang WJ,Hsu KC
Abstract : Excessive eIF4E phosphorylation by mitogen-activated protein kinase (MAPK)-interacting kinases 1 and 2 (MNK1 and MNK2; collectively, MNKs) has been associated with oncogenesis. The overexpression of eIF4E in acute myeloid leukemia (AML) is related to cancer cell growth and survival. Thus, the inhibition of MNKs and eIF4E phosphorylation are potential therapeutic strategies for AML. Herein, a structure-based virtual screening approach was performed to identify potential MNK inhibitors from natural products. Three flavonoids, apigenin, hispidulin, and luteolin, showed MNK2 inhibitory activity with IC values of 308, 252, and 579 nM, respectively. A structure-activity relationship analysis was performed to disclose the molecular interactions. Furthermore, luteolin exhibited substantial inhibitory efficacy against MNK1 (IC = 179 nM). Experimental results from cellular assays showed that hispidulin and luteolin inhibited the growth of MOLM-13 and MV4-11 AML cells by downregulating eIF4E phosphorylation and arresting the cell cycle at the G0/G1 phase. Therefore, hispidulin and luteolin showed promising results as lead compounds for the potential treatment for AML.
|
Inhibition of MNK1/MNK2 in human MOLM-13 cells assessed as reduction in eIF4E phosphorylation reduction in eIF4E phosphorylation at 10 uM after 24 to 48 hrs by Western blot analysis
|
Homo sapiens
|
100.0
%
|
|
Journal : J Nat Prod
Title : Biological Evaluation of Selected Flavonoids as Inhibitors of MNKs Targeting Acute Myeloid Leukemia.
Year : 2020
Volume : 83
Issue : 10
First Page : 2967
Last Page : 2975
Authors : Chen LC,Huang HL,HuangFu WC,Yen SC,Ngo ST,Wu YW,Lin TE,Sung TY,Lien ST,Tseng HJ,Pan SL,Huang WJ,Hsu KC
Abstract : Excessive eIF4E phosphorylation by mitogen-activated protein kinase (MAPK)-interacting kinases 1 and 2 (MNK1 and MNK2; collectively, MNKs) has been associated with oncogenesis. The overexpression of eIF4E in acute myeloid leukemia (AML) is related to cancer cell growth and survival. Thus, the inhibition of MNKs and eIF4E phosphorylation are potential therapeutic strategies for AML. Herein, a structure-based virtual screening approach was performed to identify potential MNK inhibitors from natural products. Three flavonoids, apigenin, hispidulin, and luteolin, showed MNK2 inhibitory activity with IC values of 308, 252, and 579 nM, respectively. A structure-activity relationship analysis was performed to disclose the molecular interactions. Furthermore, luteolin exhibited substantial inhibitory efficacy against MNK1 (IC = 179 nM). Experimental results from cellular assays showed that hispidulin and luteolin inhibited the growth of MOLM-13 and MV4-11 AML cells by downregulating eIF4E phosphorylation and arresting the cell cycle at the G0/G1 phase. Therefore, hispidulin and luteolin showed promising results as lead compounds for the potential treatment for AML.
|
Inhibition of biotinylated 5-(4-((Z)-3-Carboxy-3-hydroxyacryloyl)-4-(4-chlorobenzyl)piperidine-1-carbonyl)-2-((13,35-dioxo-39-((3aR,4R,6aS)-2-oxohexahydro-1H-thieno[3,4-d]imidazole-4-yl)-3,6,9,16,19,22,25,28,31-nonaoxa-12,34-diazanonatriacontyl)oxy)benzoic acid binding to Influenza A virus (A/California/07/2009(H1N1)) N-terminal GST-tagged polymerase acidic subunit N-terminal domain expressed in Escherichia coli BL21 (DE3) RIL cells measured after 120 mins by Alphascreen assay
|
Influenza A virus (A/California/07/2009(H1N1))
|
72.0
nM
|
|
Journal : Eur J Med Chem
Title : Unraveling the anti-influenza effect of flavonoids: Experimental validation of luteolin and its congeners as potent influenza endonuclease inhibitors.
Year : 2020
Volume : 208
First Page : 112754
Last Page : 112754
Authors : Zima V,Radilová K,Kožíšek M,Albiñana CB,Karlukova E,Brynda J,Fanfrlík J,Flieger M,Hodek J,Weber J,Majer P,Konvalinka J,Machara A
Abstract : The biological effects of flavonoids on mammal cells are diverse, ranging from scavenging free radicals and anti-cancer activity to anti-influenza activity. Despite appreciable effort to understand the anti-influenza activity of flavonoids, there is no clear consensus about their precise mode-of-action at a cellular level. Here, we report the development and validation of a screening assay based on AlphaScreen technology and illustrate its application for determination of the inhibitory potency of a large set of polyols against PA N-terminal domain (PA-Nter) of influenza RNA-dependent RNA polymerase featuring endonuclease activity. The most potent inhibitors we identified were luteolin with an IC of 72 ± 2 nM and its 8-C-glucoside orientin with an IC of 43 ± 2 nM. Submicromolar inhibitors were also evaluated by an in vitro endonuclease activity assay using single-stranded DNA, and the results were in full agreement with data from the competitive AlphaScreen assay. Using X-ray crystallography, we analyzed structures of the PA-Nter in complex with luteolin at 2.0 Å resolution and quambalarine B at 2.5 Å resolution, which clearly revealed the binding pose of these polyols coordinated to two manganese ions in the endonuclease active site. Using two distinct assays along with the structural work, we have presumably identified and characterized the molecular mode-of-action of flavonoids in influenza-infected cells.
|
Inhibition of LPS-induced nitric oxide production in mouse RAW264.7 cells at 10 uM measured after 24 hrs by Griess reagent based assay relative to control
|
Mus musculus
|
54.6
%
|
|
Journal : Eur J Med Chem
Title : Development of a novel nitric oxide (NO) production inhibitor with potential therapeutic effect on chronic inflammation.
Year : 2020
Volume : 193
First Page : 112216
Last Page : 112216
Authors : Yang Y,Wei Z,Teichmann AT,Wieland FH,Wang A,Lei X,Zhu Y,Yin J,Fan T,Zhou L,Wang C,Chen L
Abstract : Inflammation is a complex biological response to stimuli. Activated macrophages induced excessively release of pro-inflammatory cytokines and mediators such as endogenous radical nitric oxide (NO) play a significant role in the progression of multiple inflammatory diseases. Both natural and synthetic chalcones possess a wide range of bioactivities. In this work, thirty-nine chalcones and three related compounds, including several novel ones, based on bioactive kava chalcones were designed, synthesized and their inhibitory effects on NO production in RAW 264.7 cells were evaluated. The novel compound (E)-1-(2'-hydroxy-4',6'-dimethoxyphenyl)-3-(3-methoxy-4-(3-morpholinopropoxy)phenyl)prop-2-en-1-one (53) exhibited a better inhibitory activity (84.0%) on NO production at 10 μM (IC = 6.4 μM) with the lowest cytotoxicity (IC > 80 μM) among the tested compounds. Besides, western blot analysis indicated that compound 53 was a potent down-regulator of inducible nitric oxide synthase (iNOS) protein. Docking study revealed that compound 53 also can dock into the active site of iNOS. Furthermore, at the dose of 10 mg/kg/day, compound 53 could both significantly suppress the progression of inflammation on collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AIA) models. In addition, the structure-activity relationship (SAR) of the kava chalcones based analogs was also depicted.
|
Inhibition of cytochrome c (unknown origin) assessed as reduction in cyt c-CL complex formation at 10 uM incubated for 15 mins in presence of cardiolipin by Trp-59 fluorescence assay relative to control
|
Homo sapiens
|
84.0
%
|
|
Journal : Bioorg Med Chem
Title : A role of flavonoids in cytochrome c-cardiolipin interactions.
Year : 2021
Volume : 33
First Page : 116043
Last Page : 116043
Authors : Rice M,Wong B,Oja M,Samuels K,Williams AK,Fong J,Sapse AM,Maran U,Korobkova EA
Abstract : The processes preceding the detachment of cytochrome c (cyt c) from the inner mitochondrial membrane in intrinsic apoptosis involve peroxidation of cardiolipin (CL) catalyzed by cyt c-CL complex. In the present work, we studied the effect of 17 dietary flavonoids on the peroxidase activity of cyt c bound to liposomes. Specifically, we explored the relationship between peroxidase activity and flavonoids' (1) potential to modulate cyt c unfolding, (2) effect on the oxidation state of heme iron, (3) membrane permeability, (4) membrane binding energy, and (5) structure. The measurements revealed that flavones, flavonols, and flavanols were the strongest, while isoflavones were the weakest inhibitors of the oxidation. Flavonoids' peroxidase inhibition activity correlated positively with their potential to suppress Trp-59 fluorescence in cyt c as well as the number of OH groups. Hydrophilic flavonoids, such as catechin, having the lowest membrane permeability and the strongest binding with phosphocholine (PC) based on the quantum chemical calculations exhibited the strongest inhibition of Amplex Red (AR) peroxidation, suggesting a membrane-protective function of flavonoids at the surface. The results of the present research specify basic principles for the design of molecules that will control the catalytic oxidation of lipids in mitochondrial membranes. These principles take into account the number of hydroxyl groups and hydrophilicity of flavonoids.
|
Inhibition of cytochrome c (unknown origin) assessed as reduction in cyt c-CL peroxidase activity at 10 uM up to 20 mins in presence of cardiolipin by Amplex red staining based fluorescence assay relative to control
|
Homo sapiens
|
71.0
%
|
|
Journal : Bioorg Med Chem
Title : A role of flavonoids in cytochrome c-cardiolipin interactions.
Year : 2021
Volume : 33
First Page : 116043
Last Page : 116043
Authors : Rice M,Wong B,Oja M,Samuels K,Williams AK,Fong J,Sapse AM,Maran U,Korobkova EA
Abstract : The processes preceding the detachment of cytochrome c (cyt c) from the inner mitochondrial membrane in intrinsic apoptosis involve peroxidation of cardiolipin (CL) catalyzed by cyt c-CL complex. In the present work, we studied the effect of 17 dietary flavonoids on the peroxidase activity of cyt c bound to liposomes. Specifically, we explored the relationship between peroxidase activity and flavonoids' (1) potential to modulate cyt c unfolding, (2) effect on the oxidation state of heme iron, (3) membrane permeability, (4) membrane binding energy, and (5) structure. The measurements revealed that flavones, flavonols, and flavanols were the strongest, while isoflavones were the weakest inhibitors of the oxidation. Flavonoids' peroxidase inhibition activity correlated positively with their potential to suppress Trp-59 fluorescence in cyt c as well as the number of OH groups. Hydrophilic flavonoids, such as catechin, having the lowest membrane permeability and the strongest binding with phosphocholine (PC) based on the quantum chemical calculations exhibited the strongest inhibition of Amplex Red (AR) peroxidation, suggesting a membrane-protective function of flavonoids at the surface. The results of the present research specify basic principles for the design of molecules that will control the catalytic oxidation of lipids in mitochondrial membranes. These principles take into account the number of hydroxyl groups and hydrophilicity of flavonoids.
|
Inhibition of cytochrome c (unknown origin) assessed as reduction reduction of cyt c from its ferric state to ferrous state at 10 uM incubated for 20 mins in presence of cardiolipin by UV-vis Spectrophotometric assay relative to control
|
Homo sapiens
|
32.0
%
|
|
Journal : Bioorg Med Chem
Title : A role of flavonoids in cytochrome c-cardiolipin interactions.
Year : 2021
Volume : 33
First Page : 116043
Last Page : 116043
Authors : Rice M,Wong B,Oja M,Samuels K,Williams AK,Fong J,Sapse AM,Maran U,Korobkova EA
Abstract : The processes preceding the detachment of cytochrome c (cyt c) from the inner mitochondrial membrane in intrinsic apoptosis involve peroxidation of cardiolipin (CL) catalyzed by cyt c-CL complex. In the present work, we studied the effect of 17 dietary flavonoids on the peroxidase activity of cyt c bound to liposomes. Specifically, we explored the relationship between peroxidase activity and flavonoids' (1) potential to modulate cyt c unfolding, (2) effect on the oxidation state of heme iron, (3) membrane permeability, (4) membrane binding energy, and (5) structure. The measurements revealed that flavones, flavonols, and flavanols were the strongest, while isoflavones were the weakest inhibitors of the oxidation. Flavonoids' peroxidase inhibition activity correlated positively with their potential to suppress Trp-59 fluorescence in cyt c as well as the number of OH groups. Hydrophilic flavonoids, such as catechin, having the lowest membrane permeability and the strongest binding with phosphocholine (PC) based on the quantum chemical calculations exhibited the strongest inhibition of Amplex Red (AR) peroxidation, suggesting a membrane-protective function of flavonoids at the surface. The results of the present research specify basic principles for the design of molecules that will control the catalytic oxidation of lipids in mitochondrial membranes. These principles take into account the number of hydroxyl groups and hydrophilicity of flavonoids.
