|
Inhibition of diphenolase activity of mushroom tyrosinase at 0.055 mM
|
Agaricus bisporus
|
12.65
%
|
|
Journal : Bioorg. Med. Chem.
Title : Identification of tyrosinase inhibitors from Marrubium velutinum and Marrubium cylleneum.
Year : 2007
Volume : 15
Issue : 7
First Page : 2708
Last Page : 2714
Authors : Karioti A, Protopappa A, Megoulas N, Skaltsa H.
Abstract : Tyrosinase is a key enzyme in the production of melanins in plants and animals. Forty-five secondary metabolites isolated from Marrubium velutinum and Marrubium cylleneum belonging to the classes of flavonoids, phenylethanoid glycosides, phenolic acids and lignan glycosides were screened for their inhibitory activity against mushroom tyrosinase. Flavonoids and phenylethanoid glycosides showed moderate inhibitory activity, while phenolic acids were less active than phenylethanoid glycosides, suggesting that both phenolic groups are important for the activity.
|
Inhibition of guinea pig classical complement system assessed as hemolysis of sensitized sheep erythrocytes at 1000 uM
|
Cavia porcellus
|
54.4
%
|
|
Journal : J. Nat. Prod.
Title : In vitro anticomplementary activity of constituents from Morinda morindoides.
Year : 1995
Volume : 58
Issue : 3
First Page : 372
Last Page : 378
Authors : Cimanga K, De Bruyne T, Lasure A, Van Poel B, Pieters L, Vanden Berghe D, Vlietinck A, Kambu K, Tona L.
Abstract : In a screening program for complement classical pathway modulation, an 80% MeOH extract of the leaves of Morinda morindoides showed potent dose-dependent anticomplementary activity. Bioassay-guided chromatographic separation of the active constituents led to the isolation of ten flavonoids of which two were aglycones. The compounds were tested in vitro for their putative complement-inhibiting properties on the classical (CP) and the alternative (AP) pathways of the complement system. The results indicated that quercetin [1], quercetin 3-O-rhamnoside (quercitrin) [5], and quercetin 3-O-rutinoside (rutin) [7] showed similar anticomplementary activities (inhibition) on the CP of complement. A mixture of two kaempferol triglycosides isolated and denoted as M(015), also had a good inhibitory effect. The effects of these compounds were dose-dependent for this pathway. On the AP of complement, quercetin [1] and M(015) had, respectively, more pronounced inhibitory and activatory effects than the other tested flavonoids, but their effects were not dose-dependent for this pathway. The other isolated flavonoids showed weak effects or were inactive for both pathways.
|
Inhibition of human plasma alternative complement system assessed as hemolysis of non-sensitized rabbit erythrocytes at 1000 uM
|
Homo sapiens
|
18.0
%
|
|
Journal : J. Nat. Prod.
Title : In vitro anticomplementary activity of constituents from Morinda morindoides.
Year : 1995
Volume : 58
Issue : 3
First Page : 372
Last Page : 378
Authors : Cimanga K, De Bruyne T, Lasure A, Van Poel B, Pieters L, Vanden Berghe D, Vlietinck A, Kambu K, Tona L.
Abstract : In a screening program for complement classical pathway modulation, an 80% MeOH extract of the leaves of Morinda morindoides showed potent dose-dependent anticomplementary activity. Bioassay-guided chromatographic separation of the active constituents led to the isolation of ten flavonoids of which two were aglycones. The compounds were tested in vitro for their putative complement-inhibiting properties on the classical (CP) and the alternative (AP) pathways of the complement system. The results indicated that quercetin [1], quercetin 3-O-rhamnoside (quercitrin) [5], and quercetin 3-O-rutinoside (rutin) [7] showed similar anticomplementary activities (inhibition) on the CP of complement. A mixture of two kaempferol triglycosides isolated and denoted as M(015), also had a good inhibitory effect. The effects of these compounds were dose-dependent for this pathway. On the AP of complement, quercetin [1] and M(015) had, respectively, more pronounced inhibitory and activatory effects than the other tested flavonoids, but their effects were not dose-dependent for this pathway. The other isolated flavonoids showed weak effects or were inactive for both pathways.
|
Toxicity in Salmonella Typhimurium T98 at 600 ug/plate after 72 hrs by Ames assay in presence of Ames S-9 fraction
|
Salmonella enterica subsp. enterica serovar Typhimurium
|
20.0
%
|
|
Journal : J. Nat. Prod.
Title : Plant antimutagenic agents, 2. Flavonoids.
Year : 1988
Volume : 51
Issue : 6
First Page : 1084
Last Page : 1091
Authors : Wall ME, Wani MC, Manikumar G, Abraham P, Taylor H, Hughes TJ, Warner J, McGivney R.
Abstract : A number of known prenylated flavonoids were isolated from Psoralea corylifolia using an assay procedure based on inhibition of the mutagenic action of 2-aminoanthracene on Salmonella typhimurium (T-98). All of these compounds were toxic rather than antimutagenic or desmutagenic. Bakuchiol [17], a known prenylated phenolic terpene, was also isolated; its activity was not due to toxicity. Biochanin A [4], a known isoflavone, was similarly isolated from Cicer arientinum and was active and nontoxic. Some of the above flavonoids were studied for inhibition of the mutagenicity of several different mutagens with results depending upon the structure of the flavonoid and the mutagen.
|
Toxicity in Salmonella Typhimurium T98 at 300 ug/plate after 72 hrs by Ames assay in presence of Ames S-9 fraction
|
Salmonella enterica subsp. enterica serovar Typhimurium
|
20.0
%
|
|
Journal : J. Nat. Prod.
Title : Plant antimutagenic agents, 2. Flavonoids.
Year : 1988
Volume : 51
Issue : 6
First Page : 1084
Last Page : 1091
Authors : Wall ME, Wani MC, Manikumar G, Abraham P, Taylor H, Hughes TJ, Warner J, McGivney R.
Abstract : A number of known prenylated flavonoids were isolated from Psoralea corylifolia using an assay procedure based on inhibition of the mutagenic action of 2-aminoanthracene on Salmonella typhimurium (T-98). All of these compounds were toxic rather than antimutagenic or desmutagenic. Bakuchiol [17], a known prenylated phenolic terpene, was also isolated; its activity was not due to toxicity. Biochanin A [4], a known isoflavone, was similarly isolated from Cicer arientinum and was active and nontoxic. Some of the above flavonoids were studied for inhibition of the mutagenicity of several different mutagens with results depending upon the structure of the flavonoid and the mutagen.
|
Antimutagenic activity in Salmonella Typhimurium T98 assessed as inhibition of 2-aminoanthracene-induced mutation at 600 ug/plate after 72 hrs in presence of Ames S-9 fraction
|
Salmonella enterica subsp. enterica serovar Typhimurium
|
0.0
%
|
|
Journal : J. Nat. Prod.
Title : Plant antimutagenic agents, 2. Flavonoids.
Year : 1988
Volume : 51
Issue : 6
First Page : 1084
Last Page : 1091
Authors : Wall ME, Wani MC, Manikumar G, Abraham P, Taylor H, Hughes TJ, Warner J, McGivney R.
Abstract : A number of known prenylated flavonoids were isolated from Psoralea corylifolia using an assay procedure based on inhibition of the mutagenic action of 2-aminoanthracene on Salmonella typhimurium (T-98). All of these compounds were toxic rather than antimutagenic or desmutagenic. Bakuchiol [17], a known prenylated phenolic terpene, was also isolated; its activity was not due to toxicity. Biochanin A [4], a known isoflavone, was similarly isolated from Cicer arientinum and was active and nontoxic. Some of the above flavonoids were studied for inhibition of the mutagenicity of several different mutagens with results depending upon the structure of the flavonoid and the mutagen.
|
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 Saccharomyces cerevisiae fatty acid synthase
|
Saccharomyces cerevisiae
|
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 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
|
30.0
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.
|
Antiprotozoal activity against Entamoeba histolytica HM-1:IMSS trophozoites after 48 hrs by MTT/PMS assay
|
Entamoeba histolytica HM-1:IMSS
|
119.7
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Antiprotozoal activity of the constituents of Conyza filaginoides.
Year : 2001
Volume : 64
Issue : 5
First Page : 671
Last Page : 673
Authors : Calzada F, Cedillo-Rivera R, Mata R.
Abstract : Bioassay-guided fractionation of the antiprotozoal extract of Conyza filaginoides led to the isolation of three new flavonol caffeoyl glycosides, namely, kaempferol 3-O-(6' '-O-E-caffeoyl)-beta-D-galactopyranoside (1), isorhamnetin 3-O-(6' '-O-E-caffeoyl)-beta-D-galactopyranoside (2), and quercetin 3-O-(6' '-O-E-caffeoyl)-beta-D-glucopyranoside (3). In addition, seven known compounds, erythrodiol (4), beta-caryophyllene-4,5-alpha-oxide (5), astragalin (6), isoquercitrin (7), nicotiflorin (8), narcissin (9), and rutin (10), were obtained. The structures of the new isolates were elucidated by spectroscopic and chemical methods. Compounds were also assessed for antiamoebic and antigiardial activities, but none was significantly active compared to the standard drugs evaluated.
|
Antiprotozoal activity against Giardia lamblia IMSS:0989:1 after 48 hrs by MTT/PMS assay
|
Giardia intestinalis
|
178.7
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Antiprotozoal activity of the constituents of Conyza filaginoides.
Year : 2001
Volume : 64
Issue : 5
First Page : 671
Last Page : 673
Authors : Calzada F, Cedillo-Rivera R, Mata R.
Abstract : Bioassay-guided fractionation of the antiprotozoal extract of Conyza filaginoides led to the isolation of three new flavonol caffeoyl glycosides, namely, kaempferol 3-O-(6' '-O-E-caffeoyl)-beta-D-galactopyranoside (1), isorhamnetin 3-O-(6' '-O-E-caffeoyl)-beta-D-galactopyranoside (2), and quercetin 3-O-(6' '-O-E-caffeoyl)-beta-D-glucopyranoside (3). In addition, seven known compounds, erythrodiol (4), beta-caryophyllene-4,5-alpha-oxide (5), astragalin (6), isoquercitrin (7), nicotiflorin (8), narcissin (9), and rutin (10), were obtained. The structures of the new isolates were elucidated by spectroscopic and chemical methods. Compounds were also assessed for antiamoebic and antigiardial activities, but none was significantly active compared to the standard drugs evaluated.
|
Inhibition of TPA-induced EBV-early antigen activation in human Raji cells relative to TPA
|
Human herpesvirus 4
|
578.0
molar ratio
|
|
Journal : J. Nat. Prod.
Title : Anti-inflammatory, anti-tumor-promoting, and cytotoxic activities of constituents of marigold (Calendula officinalis) flowers.
Year : 2006
Volume : 69
Issue : 12
First Page : 1692
Last Page : 1696
Authors : Ukiya M, Akihisa T, Yasukawa K, Tokuda H, Suzuki T, Kimura Y.
Abstract : Ten oleanane-type triterpene glycosides, 1-10, including four new compounds, calendulaglycoside A 6'-O-methyl ester (2), calendulaglycoside A 6'-O-n-butyl ester (3), calendulaglycoside B 6'-O-n-butyl ester (5), and calendulaglycoside C 6'-O-n-butyl ester (8), along with five known flavonol glycosides, 11-15, were isolated from the flowers of marigold (Calendula officinalis). Upon evaluation of compounds 1-9 for inhibitory activity against 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation (1 microg/ear) in mice, all of the compounds, except for 1, exhibited marked anti-inflammatory activity, with ID50 values of 0.05-0.20 mg per ear. In addition, when 1-15 were evaluated against the Epstein-Barr virus early antigen (EBV-EA) activation induced by TPA, compounds 1-10 exhibited moderate inhibitory effects (IC50 values of 471-487 mol ratio/32 pmol TPA). Furthermore, upon evaluation of the cytotoxic activity against human cancer cell lines in vitro in the NCI Developmental Therapeutics Program, two triterpene glycosides, 9 and 10, exhibited their most potent cytotoxic effects against colon cancer, leukemia, and melanoma cells.
|
Antioxidant activity assessed as DPPH radical scavenging activity after 20 mins by UV-visible spectrophotometry
|
None
|
4.8
ug
|
|
Journal : J. Nat. Prod.
Title : An extract of Tagetes lucida and its phenolic constituents as antioxidants.
Year : 2002
Volume : 65
Issue : 12
First Page : 1773
Last Page : 1776
Authors : Aquino R, Cáceres A, Morelli S, Rastrelli L.
Abstract : Analysis of a methanolic extract of Tagetes lucida leaves has resulted in the isolation of a new flavonol glycoside, quercetagenin 3,4'-dimethyl ether 7-O-beta-D-glucopyranoside (1), two new phenolic acids, 3-(2-O-beta-D-glucopyranosyl-4-methoxyphenyl)propanoic acid (2) and its methylester (3), and known flavonols, aromatic acids, and 7-methoxycoumarin. Using the DPPH degrees test, the extract and some of its constituents showed a significant free-radical-scavenging effect in comparison to alpha-tocopherol and standard flavonols.
|
Inhibition of theophylline-stimulated melanogenesis in mouse B16-4A5 cells at 30 uM after 72 hrs
|
Mus musculus
|
5.2
%
|
|
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 theophylline-stimulated melanogenesis in mouse B16-4A5 cells at 10 uM after 72 hrs
|
Mus musculus
|
4.3
%
|
|
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
|
3.1
%
|
|
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 1 uM after 72 hrs
|
Mus musculus
|
4.5
%
|
|
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.
|
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
|
8.8
%
|
|
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.
|
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))
|
31.14
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.
|
Antioxidant activity assessed as DPPH free radical scavenging activity
|
None
|
15.5
ug
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis and antioxygenic activities of seabuckthorn flavone-3-ols and analogs.
Year : 2011
Volume : 21
Issue : 18
First Page : 5328
Last Page : 5330
Authors : Pandurangan N, Bose C, Banerji A.
Abstract : A practical synthesis of polyhydroxy- and regiospecifically methylated flavone-3-ols which are components of commercial 'seabuckthorn flavone' has been achieved by modified Algar-Flynn-Oyamada method. Antioxidant activities of seabuckthorn extracts, isolated products and a number of flavone-3-ols have been determined. Structure-activity relationships have been discussed. Amongst the compounds tested, gallic acid, which is also present in seabuckthorn, was found to be the most effective antioxidant and radioprotectant.
|
Inhibition of bovine kidney LMW-PTPase at 400 uM using pNPP substrate
|
Bos taurus
|
14.0
%
|
|
Journal : J. Med. Chem.
Title : Low molecular weight phosphotyrosine protein phosphatases as emerging targets for the design of novel therapeutic agents.
Year : 2012
Volume : 55
Issue : 1
First Page : 2
Last Page : 22
Authors : Maccari R, Ottanà R.
|
Inhibition of electric eel AChE at 2 mg/ml by Ellman's method
|
Electrophorus electricus
|
-0.25
%
|
|
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
|
4.32
%
|
|
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.
|
Antioxidant activity assessed as inhibition of xanthine-xanthine oxidase generated superoxide anion radical production at 200 ug/ml after 30 min by NBT reduction assay
|
None
|
35.0
%
|
|
Journal : Med Chem Res
Title : Lipid lowering and antioxidant activity of flavones in triton treated hyperlipidemic rats
Year : 2011
Volume : 20
Issue : 9
First Page : 1622
Last Page : 1626
Authors : Bhatia G, Khanna AK, Sonkar R, Mishra SK, Srivastava S, Lakshmi V
|
Antioxidant activity assessed as inhibition of xanthine-xanthine oxidase generated superoxide anion radical production at 100 ug/ml after 30 min by NBT reduction assay
|
None
|
18.0
%
|
|
Journal : Med Chem Res
Title : Lipid lowering and antioxidant activity of flavones in triton treated hyperlipidemic rats
Year : 2011
Volume : 20
Issue : 9
First Page : 1622
Last Page : 1626
Authors : Bhatia G, Khanna AK, Sonkar R, Mishra SK, Srivastava S, Lakshmi V
|
Antifungal activity against Verticillium dahliae assessed as inhibition of mycelial radial growth measured after 350 hr
|
Verticillium dahliae
|
80.0
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. .
|
Antioxidant activity assessed as ABTS radical scavenging activity
|
None
|
4.65
ug.mL-1
|
|
Journal : Med Chem Res
Title : In vitro antioxidant properties and in vivo lowering blood lipid of Forsythia suspense leaves
Year : 2010
Volume : 19
Issue : 7
First Page : 617
Last Page : 628
Authors : Kang W, Wang J
|
Antioxidant activity assessed as DPPH radical scavenging activity after 30 min
|
None
|
1.83
ug.mL-1
|
|
Journal : Med Chem Res
Title : In vitro antioxidant properties and in vivo lowering blood lipid of Forsythia suspense leaves
Year : 2010
Volume : 19
Issue : 7
First Page : 617
Last Page : 628
Authors : Kang W, Wang J
|
Antiamoebic activity against Entamoeba histolytica
|
Entamoeba histolytica
|
120.7
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
|
Inhibition of trypsin (unknown origin) using BApNA as substrate at 2 mg/ml incubated for 15 min prior to substrate addition measured after 30 min by UV/VIS spectrophotometric analysis
|
Homo sapiens
|
75.2
%
|
|
Journal : Med Chem Res
Title : Trypsin inhibitory potential and microbial transformation of rutin isolated from Citrus sinensis
Year : 2013
Volume : 22
Issue : 8
First Page : 3698
Last Page : 3702
Authors : Raza MA, Shahwar D
|
Inhibition of AChE (unknown origin)
|
Homo sapiens
|
12.0
nM
|
|
Journal : Med Chem Res
Title : Flavonoids as lead compounds modulating the enzyme targets in Alzheimers disease
Year : 2013
Volume : 22
Issue : 7
First Page : 3061
Last Page : 3075
Authors : Anand P, Singh B
|
Inhibition of TRAP activity in RANKL-induced Balb/c mouse RAW264.7 cells at 10 uM after 1 hr by ELISA relative to control
|
Mus musculus
|
71.68
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Identification and biological evaluation of flavonoids from the fruits of Prunus mume.
Year : 2014
Volume : 24
Issue : 5
First Page : 1397
Last Page : 1402
Authors : Yan XT, Li W, Sun YN, Yang SY, Lee SH, Chen JB, Jang HD, Kim YH.
Abstract : This Letter describes the identification of potent antioxidant and anti-osteoporosis agents from the fruits of Prunus mume. From the methanol extract, a novel flavan dimer, characterized as 2β,3β-epoxy-5,7,4'-trihydroxyflavan-(4α→8)-epicatechin (1), was isolated along with five known flavonoids (2-6). Their structures were determined based on extensive spectroscopic analysis, including IR, HRESIMS, 1D- and 2D-NMR, and CD spectra. The antioxidant activities of compounds 1-6 were evaluated in terms of their peroxyl radical-scavenging (Trolox equivalent) and reducing capacities. All isolates showed potent peroxyl radical-scavenging and reducing activities at concentrations of 1-10 μM. Among them, compounds 1 and 2 were the most active at 1 μM. Anti-osteoporosis activities were investigated using both murine osteoblastic MC3T3-E1 cells and osteoclastic RAW 264.7 cells. Compounds 2, 3, and 6 significantly stimulated the differentiation of osteoblastic MC3T3-E1 cells to increase collagen synthesis or mineralization functions of osteoblasts. Compounds 1, 3, 4, and 6 significantly suppressed tartrate-resistant acid phosphatase (TRAP) activity in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastic RAW 264.7 macrophage cells.
|
Inhibition of TRAP activity in Balb/c mouse RAW264.7 cells at 10 uM after 1 hr by ELISA relative to control
|
Mus musculus
|
145.67
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Identification and biological evaluation of flavonoids from the fruits of Prunus mume.
Year : 2014
Volume : 24
Issue : 5
First Page : 1397
Last Page : 1402
Authors : Yan XT, Li W, Sun YN, Yang SY, Lee SH, Chen JB, Jang HD, Kim YH.
Abstract : This Letter describes the identification of potent antioxidant and anti-osteoporosis agents from the fruits of Prunus mume. From the methanol extract, a novel flavan dimer, characterized as 2β,3β-epoxy-5,7,4'-trihydroxyflavan-(4α→8)-epicatechin (1), was isolated along with five known flavonoids (2-6). Their structures were determined based on extensive spectroscopic analysis, including IR, HRESIMS, 1D- and 2D-NMR, and CD spectra. The antioxidant activities of compounds 1-6 were evaluated in terms of their peroxyl radical-scavenging (Trolox equivalent) and reducing capacities. All isolates showed potent peroxyl radical-scavenging and reducing activities at concentrations of 1-10 μM. Among them, compounds 1 and 2 were the most active at 1 μM. Anti-osteoporosis activities were investigated using both murine osteoblastic MC3T3-E1 cells and osteoclastic RAW 264.7 cells. Compounds 2, 3, and 6 significantly stimulated the differentiation of osteoblastic MC3T3-E1 cells to increase collagen synthesis or mineralization functions of osteoblasts. Compounds 1, 3, 4, and 6 significantly suppressed tartrate-resistant acid phosphatase (TRAP) activity in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastic RAW 264.7 macrophage cells.
|
Inhibition of TRAP activity in RANKL-induced Balb/c mouse RAW264.7 cells at 1 uM after 1 hr by ELISA relative to control
|
Mus musculus
|
78.02
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Identification and biological evaluation of flavonoids from the fruits of Prunus mume.
Year : 2014
Volume : 24
Issue : 5
First Page : 1397
Last Page : 1402
Authors : Yan XT, Li W, Sun YN, Yang SY, Lee SH, Chen JB, Jang HD, Kim YH.
Abstract : This Letter describes the identification of potent antioxidant and anti-osteoporosis agents from the fruits of Prunus mume. From the methanol extract, a novel flavan dimer, characterized as 2β,3β-epoxy-5,7,4'-trihydroxyflavan-(4α→8)-epicatechin (1), was isolated along with five known flavonoids (2-6). Their structures were determined based on extensive spectroscopic analysis, including IR, HRESIMS, 1D- and 2D-NMR, and CD spectra. The antioxidant activities of compounds 1-6 were evaluated in terms of their peroxyl radical-scavenging (Trolox equivalent) and reducing capacities. All isolates showed potent peroxyl radical-scavenging and reducing activities at concentrations of 1-10 μM. Among them, compounds 1 and 2 were the most active at 1 μM. Anti-osteoporosis activities were investigated using both murine osteoblastic MC3T3-E1 cells and osteoclastic RAW 264.7 cells. Compounds 2, 3, and 6 significantly stimulated the differentiation of osteoblastic MC3T3-E1 cells to increase collagen synthesis or mineralization functions of osteoblasts. Compounds 1, 3, 4, and 6 significantly suppressed tartrate-resistant acid phosphatase (TRAP) activity in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastic RAW 264.7 macrophage cells.
|
Inhibition of TRAP activity in Balb/c mouse RAW264.7 cells at 1 uM after 1 hr by ELISA relative to control
|
Mus musculus
|
158.55
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Identification and biological evaluation of flavonoids from the fruits of Prunus mume.
Year : 2014
Volume : 24
Issue : 5
First Page : 1397
Last Page : 1402
Authors : Yan XT, Li W, Sun YN, Yang SY, Lee SH, Chen JB, Jang HD, Kim YH.
Abstract : This Letter describes the identification of potent antioxidant and anti-osteoporosis agents from the fruits of Prunus mume. From the methanol extract, a novel flavan dimer, characterized as 2β,3β-epoxy-5,7,4'-trihydroxyflavan-(4α→8)-epicatechin (1), was isolated along with five known flavonoids (2-6). Their structures were determined based on extensive spectroscopic analysis, including IR, HRESIMS, 1D- and 2D-NMR, and CD spectra. The antioxidant activities of compounds 1-6 were evaluated in terms of their peroxyl radical-scavenging (Trolox equivalent) and reducing capacities. All isolates showed potent peroxyl radical-scavenging and reducing activities at concentrations of 1-10 μM. Among them, compounds 1 and 2 were the most active at 1 μM. Anti-osteoporosis activities were investigated using both murine osteoblastic MC3T3-E1 cells and osteoclastic RAW 264.7 cells. Compounds 2, 3, and 6 significantly stimulated the differentiation of osteoblastic MC3T3-E1 cells to increase collagen synthesis or mineralization functions of osteoblasts. Compounds 1, 3, 4, and 6 significantly suppressed tartrate-resistant acid phosphatase (TRAP) activity in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastic RAW 264.7 macrophage cells.
|
Inhibition of sEH (unknown origin) assessed as substrate PHOME hydrolysis at 25 uM after 1 hr by fluorescence method
|
Homo sapiens
|
40.0
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Anti-inflammatory components of Euphorbia humifusa Willd.
Year : 2014
Volume : 24
Issue : 8
First Page : 1895
Last Page : 1900
Authors : Luyen BT, Tai BH, Thao NP, Eun KJ, Cha JY, Xin MJ, Lee YM, Kim YH.
Abstract : Two new compounds, euphorbinoside (1) and dehydropicrorhiza acid methyl diester (2), along with 24 known compounds (3-26) were isolated from Euphorbia humifusa Willd. The effects of these compounds on soluble epoxide hydrolase (sEH) inhibitory activity were evaluated. Flavonoid compounds (10-21) exhibited high sEH inhibitory activity. Among them, compounds 12, 13, and 19 greatly inhibited sEH enzymatic activity, with IC50 values as low as 18.05±1.17, 18.64±1.83, and 17.23±0.84 μM, respectively. In addition, the effects of these compounds on lipopolysaccharide (LPS)-induced nitric oxide (NO) and tumor necrosis factor alpha (TNF-α) production by RAW 264.7 cells were investigated. Compounds 3-6, 8, 18, 20-23, and 25-26 inhibited the production of both NO and TNF-α, with IC50 values ranging from 11.1±0.9 to 45.3±1.6 μM and 14.4±0.5 to 44.5±1.2 μM, respectively.
|
Inhibition of alpha-amylase (unknown origin) relative to control
|
Homo sapiens
|
20.1
%
|
|
Journal : Bioorg. Med. Chem.
Title : From carbohydrates to drug-like fragments: Rational development of novel α-amylase inhibitors.
Year : 2015
Volume : 23
Issue : 20
First Page : 6725
Last Page : 6732
Authors : Al-Asri J, Fazekas E, Lehoczki G, Perdih A, Görick C, Melzig MF, Gyémánt G, Wolber G, Mortier J.
Abstract : Starch catabolism leading to high glucose level in blood is highly problematic in chronic metabolic diseases, such as type II diabetes and obesity. α-Amylase catalyzes the hydrolysis of starch, increasing blood sugar concentration. Its inhibition represents a promising therapeutic approach to control hyperglycaemia. However, only few drug-like molecule inhibitors without sugar moieties have been discovered so far, and little information on the enzymatic mechanism is available. This work aims at the discovery of novel small α-amylase binders using a systematic in silico methodology. 3D-pharmacophore-based high throughput virtual screening of small compounds libraries was performed to identify compounds with high α-amylase affinity. Twenty-seven compounds were selected and biologically tested, revealing IC50 values in the micromolar range and ligand efficiency higher than the one of the bound form of acarbose, which is used as a reference for α-amylase inhibition.
|
Inhibition of Mycobacterium tuberculosis MTCC 300 DAH7PS expressed in Escherichia coli BL21 (DE3) using 25 to 125 uM PEP/100 uM E4P as substrate at 10 uM by spectrophotometric analysis relative to control
|
Mycobacterium tuberculosis
|
17.0
%
|
|
Journal : Eur. J. Med. Chem.
Title : Inhibition of 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase from Mycobacterium tuberculosis: in silico screening and in vitro validation.
Year : 2015
Volume : 105
First Page : 182
Last Page : 193
Authors : Nirmal CR, Rao R, Hopper W.
Abstract : Tuberculosis, caused by Mycobacterium tuberculosis, remains a serious global health threat, highlighting the urgent need for novel antituberculosis drugs. The shikimate pathway, responsible for aromatic amino acid biosynthesis, is required for the growth of Mycobacterium tuberculosis and is a potential drug target. 3-deoxy-D-arabino-heptulosonate 7-phosphate synthase (mtDAH7Ps) catalyzes the first step in shikimate pathway. E-pharmacophore models for inhibitors of mtDAH7Ps - tyrosine, phenylalanine, phosphoenolpyruvate and (2S)-2,7-bis(phosphonooxy)heptanoic acid were screened against ZINC synthetic and natural compounds databases. The shortlisted compounds were subjected to induce fit docking and validated by Prime/Molecular Mechanics Generalized Born Surface Area calculation to predict ligand binding energy and ligand strain energy for ligand and receptor. The lead compounds were screened for their inhibitory activity against purified mtDAH7Ps enzyme. Lead compounds inhibited mtDAH7Ps in a concentration-dependent manner; with an IC50 value of 21 μM, 42 μM and 54 μM for α-Tocopherol, rutin and 3-Pyridine carboxyaldehyde respectively. Molecular Dynamics analysis for 50 ns of the active compounds-mtDAH7Ps complexes showed that the backbone of mtDAH7Ps was stable. These results suggest that α-tocopherol, 3 - Pyridine carboxyaldehyde and rutin could be novel drug leads to inhibit mtDAH7Ps in M. tuberculosis.
|
Antibacterial activity against Staphylococcus aureus MRSA ATCC 43300 (CO-ADD:GP_020); MIC in CAMBH media, using NBS plates, by OD(600)
|
Staphylococcus aureus subsp. aureus
|
17.86
%
|
|
|
Antibacterial activity against Escherichia coli ATCC 25922 (CO-ADD:GN_001); MIC in CAMBH media using NBS plates, by OD(600)
|
Escherichia coli
|
2.05
%
|
|
|
Antibacterial activity against Klebsiella pneumoniae MDR ATCC 70063 (CO-ADD:GN_003); MIC in CAMBH media using NBS plates, by OD(600)
|
Klebsiella pneumoniae
|
10.13
%
|
|
|
Antibacterial activity against Pseudomonas aeruginosa ATCC 27853 (CO-ADD:GN_042); MIC in CAMBH media using NBS plates, by OD(600)
|
Pseudomonas aeruginosa
|
17.85
%
|
|
|
Antibacterial activity against Acinetobacter baumannii ATCC 19606 (CO-ADD:GN_034); MIC in CAMBH media using NBS plates, by OD600
|
Acinetobacter baumannii
|
25.94
%
|
|
|
Antifungal activity against Candida albicans ATCC 90028 (CO-ADD:FG_001); MIC in YNB media using NBS plates, by OD630
|
Candida albicans
|
3.37
%
|
|
|
Antifungal activity against Cryptococcus neoformans H99 ATCC 208821 (CO-ADD:FG_002); MIC in YNB media using NBS plates, by Resazurin OD(600-570)
|
Cryptococcus neoformans
|
-5.7
%
|
|
|
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
|
40.82
%
|
|
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 Enterobacter cloacae beta-lactamase at 500 uM incubated for 10 mins followed by nitrocefin substrate challenge and measured for 5 mins by spectrophotometric analysis relative to control
|
Enterobacter cloacae
|
15.0
%
|
|
Journal : ACS Med Chem Lett
Title : DMSO-Perturbing Assay for Identifying Promiscuous Enzyme Inhibitors.
Year : 2019
Volume : 10
Issue : 6
First Page : 923
Last Page : 928
Authors : Tomohara K, Adachi I, Horino Y, Kesamaru H, Abe H, Suyama K, Nose T.
Abstract : In search for enzyme inhibitors, we often encounter "promiscuous" enzyme inhibitors exhibiting nonspecific binding property toward enzyme active site. Therefore, inhibitory candidates should be mechanistically characterized as early as possible in discovery processes. However, there remains a lack of highly reliable and readily available methodology to evaluate specificity of initial hits inhibitors. The present study developed and established a novel DMSO-perturbing assay to identify promiscuous enzyme inhibitors. The assay successfully identified nonspecific binding inhibitors with a broad scope, typically by the attenuation of inhibitory activity by the influence of DMSO-addition. This attenuation would be attributed to the nonspecific binding property of inhibitors toward both productive and nonproductive (nondenatured) states of enzymes in perturbation solution. This working hypothesis was supported by spectroscopic analyses of enzyme conformations and analyses of solvent effects on perturbation. Overall, these results provided a novel concept of the DMSO-perturbing assay.
|
Anti-colitis activity in ICR mouse model of DSS-induced colitis assessed as inhibition of DSS-induced colorectum shortening at 6 mg, po for 14 days relative to control
|
Mus musculus
|
73.0
%
|
|
Journal : Eur J Med Chem
Title : Discovery of small-molecule candidates against inflammatory bowel disease.
Year : 2020
Volume : 185
First Page : 111805
Last Page : 111805
Authors : Bai R, Jie X, Yao C, Xie Y.
Abstract : Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disease in the gastrointestinal tract emerged as a public health challenge worldwide. IBD exhibits a relapsing and remitting course results in negative impacts on both physical and psychological health of IBD patients. Great efforts have been made during the past few years, but relatively limited drugs are currently available for the management of IBD. Clinically, there is a strong demand for new drugs for the treatment of IBD with better efficacy and lower side effects. This review focuses on the drug discovery process of the anti-IBD agents, aiming to introduce the general characteristics of IBD, as well as systematically summarize the recent advances in the discovery of small-molecule candidates and natural products with promising in vivo potential for the treatment of IBD.
|
Inhibition of F1F0-ATP synthase in Escherichia coli after 60 mins relative to control
|
Escherichia coli
|
40.0
%
|
|
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.
|
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate
|
Severe acute respiratory syndrome coronavirus 2
|
12.75
%
|
|
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.
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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
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Chlorocebus sabaeus
|
-0.08
%
|
|
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
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Chlorocebus sabaeus
|
-0.08
%
|
|
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.
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Inhibition of human liver FBP1 at 200 uM incubated for 5 mins by fluorescence method relative to control
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Homo sapiens
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20.0
%
|
|
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.
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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
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Homo sapiens
|
66.0
%
|
|
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.
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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
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Homo sapiens
|
28.0
%
|
|
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.
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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
|
19.0
%
|
|
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.
