|
Antioxidant activity assessed as superoxide anion radical scavenging activity
|
None
|
530.0
nM
|
|
Journal : J. Nat. Prod.
Title : Structures and radical-scavenging activities of phenolic constituents from the bark of Picea jezoensis var. jezoensis.
Year : 2007
Volume : 70
Issue : 10
First Page : 1605
Last Page : 1610
Authors : Wada S, Yasui Y, Hitomi T, Tanaka R.
Abstract : The MeOH extract of the bark of Picea jezoensis var. jezoensis was found to show scavenging activity for the DPPH radical. Bioassay-guided fractionation led to the isolation of two new flavonostilbenes named jezonocinols A ( 1) and B ( 2) and one nor-flavonostilbene named jezonocinol C ( 3) together with six known phenolic compounds. Their structures were elucidated by spectroscopic methods, and the absolute configurations of jezonocinols A ( 1) and B ( 2) were determined by Mosher's method, CD, and NOESY data.
|
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 NADPH oxidase in LPS-induced mouse BV2 cells assessed as NOX-dependent ROS production at 50 uM
|
Mus musculus
|
21.5
%
|
|
Journal : Bioorg. Med. Chem.
Title : New diterpenoids and the bioactivity of Erythrophleum fordii.
Year : 2008
Volume : 16
Issue : 22
First Page : 9867
Last Page : 9870
Authors : Tsao CC, Shen YC, Su CR, Li CY, Liou MJ, Dung NX, Wu TS.
Abstract : A phytochemical investigation of the leaves of Erythrophleum fordii Oliv. has led to the isolation of three new cassaine-type diterpenoids, erythrofordin A (1), erythrofordin B (2) and erythrofordin C (3), as well as a norcassaine diterpenoid with a novel skeleton, norerythrofordin A (4), and 27 known compounds (5-31). The structures of 1-4 were elucidated on the basis of spectroscopic analysis. Selected compounds from this plant were examined for anti-inflammatory activity. Taraxerol (16) displayed potent NO-reducing activity in microglial cells, and gallic acid (27) exhibited excellent DPPH radical-scavenging effects.
|
Antiplasmodial activity after 24 hrs against chloroquine-sensitive, mefloquine-resistant Plasmodium falciparum D6 infected human erythrocytes by [G-3H]hypoxanthine uptake
|
Plasmodium falciparum D6
|
5.0
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : In vitro antiplasmodial activity of extracts of Tristaniopsis species and identification of the active constituents: ellagic acid and 3,4,5-trimethoxyphenyl-(6'-O-galloyl)-O-beta-D-glucopyranoside.
Year : 2001
Volume : 64
Issue : 5
First Page : 603
Last Page : 607
Authors : Verotta L, Dell'Agli M, Giolito A, Guerrini M, Cabalion P, Bosisio E.
Abstract : Screening of plants from New Caledonia for antiplasmodial activity against Plasmodium falciparum revealed that methanolic extracts of the leaves and bark of Tristaniopsis calobuxus, T. yateensis, and T.glauca inhibited the growth of chloroquine-sensitive and -resistant clones. Ellagic acid and the new compound 3,4,5-trimethoxyphenyl-(6'-O-galloyl)-O-beta-D-glucopyranoside were identified as the active constituents (IC50 0.5 and 3.2 microM, respectively). The growth inhibition of both clones was comparable. The compounds showed negligible or very low cytotoxicity to human skin fibroblasts and Hep G2 cells when tested at concentrations ranging from 0.5 to 100 microM.
|
Antibabesial activity against Babesia gibsoni in dog erythrocytes after 72 hrs
|
Babesia gibsoni
|
13.4
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Anti-babesial and anti-plasmodial compounds from Phyllanthus niruri.
Year : 2005
Volume : 68
Issue : 4
First Page : 537
Last Page : 539
Authors : Subeki S, Matsuura H, Takahashi K, Yamasaki M, Yamato O, Maede Y, Katakura K, Kobayashi S, Trimurningsih T, Chairul C, Yoshihara T.
Abstract : Bioassay-guided fractionation of boiled aqueous extracts from the whole plant of Phyllanthus niruri led to the isolation of 1-O-galloyl-6-O-luteoyl-alpha-d-glucose (1), with IC(50) values of 4.7 microg/mL against Babesia gibsoni and 1.4 microg/mL against Plasmodium falciparum in vitro. The known compounds beta-glucogallin (2), quercetin 3-O-beta-d-glucopyranosyl-(2-->1)-O-beta-d-xylopyranoside (3), beta-sitosterol, and gallic acid were also isolated. Structures of these compounds were elucidated on the basis of their chemical and spectroscopic data.
|
Antiplasmodial activity against chloroquine-susceptible Plasmodium falciparum FCR3 in human erythrocytes after 24 hrs
|
Plasmodium falciparum
|
14.8
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Anti-babesial and anti-plasmodial compounds from Phyllanthus niruri.
Year : 2005
Volume : 68
Issue : 4
First Page : 537
Last Page : 539
Authors : Subeki S, Matsuura H, Takahashi K, Yamasaki M, Yamato O, Maede Y, Katakura K, Kobayashi S, Trimurningsih T, Chairul C, Yoshihara T.
Abstract : Bioassay-guided fractionation of boiled aqueous extracts from the whole plant of Phyllanthus niruri led to the isolation of 1-O-galloyl-6-O-luteoyl-alpha-d-glucose (1), with IC(50) values of 4.7 microg/mL against Babesia gibsoni and 1.4 microg/mL against Plasmodium falciparum in vitro. The known compounds beta-glucogallin (2), quercetin 3-O-beta-d-glucopyranosyl-(2-->1)-O-beta-d-xylopyranoside (3), beta-sitosterol, and gallic acid were also isolated. Structures of these compounds were elucidated on the basis of their chemical and spectroscopic data.
|
Antioxidant activity assessed as DPPH radical scavenging activity after 30 mins
|
None
|
10.0
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Activity-guided isolation of antioxidative constituents of Cotinus coggygria.
Year : 2000
Volume : 63
Issue : 12
First Page : 1696
Last Page : 1698
Authors : Westenburg HE, Lee KJ, Lee SK, Fong HH, van Breemen RB, Pezzuto JM, Kinghorn AD.
Abstract : Six constituents (1-6) were isolated from EtOAc-soluble partitions of two separate collections of the whole plants of Cotinus coggygria, namely, disulfuretin ¿2,2'-[1,2-bis(3,4-dihydroxyphenyl)-1, 2-ethanedylidene]bis[6-hydroxy-3(2H)-benzofuranone] (1)¿, sulfuretin (2), sulfurein (3), gallic acid (4), methyl gallate (5), and pentagalloyl glucose (6). The structure of the novel biaurone 1 was determined by spectral and chemical methods. Compounds 1-6 were found to be potent antioxidants in a 1,1-diphenyl-2-picrylhydrazyl free-radical scavenging assay.
|
Antioxidant activity assessed as DPPH free radical scavenging activity
|
None
|
3.7
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
|
3.2
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.
|
Inhibition of soybean 15-lipoxygenase
|
Glycine max
|
60.5
%
|
|
Journal : Bioorg. Med. Chem.
Title : Inhibition of 15-lipoxygenase-catalysed oxygenation of arachidonic acid by substituted benzoic acids.
Year : 2008
Volume : 16
Issue : 8
First Page : 4589
Last Page : 4593
Authors : Russell WR, Scobbie L, Duthie GG, Chesson A.
Abstract : Elevated levels of phospholipases, prostaglandin synthases and lipoxygenases in colonic cells at various stages of malignancy indicate a strong link between dietary lipids and colon cancer. Lipoxygenase-catalysed arachidonic acid metabolism plays a key role in colorectal carcinogenesis and has the potential to be modulated by phenolic compounds. Plant-based foods are rich sources of phenolic compounds and in the human colon they are predominantly available as simple phenolics such as the benzoic acids. Benzoic acids were determined in faecal waters from four volunteers consuming a western-style diet. Structure-activity relationships were established for the lipoxygenase-catalysed oxygenation of arachidonic acid using an oxygen electrode. All compounds studied inhibited this reaction (21-73%; p<0.001) and many of the structural features could be rationalised by computational modelling. No correlation was observed with the ability to act as reductants, supporting the hypothesis that their mode of inhibition may not be by a direct redox effect on the non-haem iron.
|
Inhibition of cataracted human eye lens aldose reductase
|
Homo sapiens
|
97.3
ug.mL-1
|
|
Journal : Bioorg. Med. Chem.
Title : Inhibition of aldose reductase from cataracted eye lenses by finger millet (Eleusine coracana) polyphenols.
Year : 2008
Volume : 16
Issue : 23
First Page : 10085
Last Page : 10090
Authors : Chethan S, Dharmesh SM, Malleshi NG.
Abstract : Retinopathy is a major cause of blindness in the Western world, while cataract is one of the three major causes of blindness worldwide. Diabetes is one of the major risk factor in retinopathy and cataract. The prevalence of blindness in India is 15 per 1000 while cataract alone accounts for 80% of this blindness. Diabetes induced cataract is characterized by an accumulation of sorbitol which is mediated by the action of a key enzyme aldose reductase (AR). Non-enzymatic glycation (binding of glucose to protein molecule) induced during diabetes appear to be the key factor for AR mediated sugar-induced cataract. Finger millet polyphenols (FMP) being a major anti-diabetic and antioxidant component, we have evaluated them for AR inhibiting activity. Phenolic constituents in FMP such as gallic, protocatechuic, p-hydroxy benzoic, p-coumaric, vanillic, syringic, ferulic, trans-cinnamic acids and the quercetin inhibited cataract eye lens effectively, the latter was more potent with an IC(50) of 14.8nM. Structure function analysis revealed that phenolics with OH group at 4th position was important for aldose reductase inhibitory property. Also the presence of neighboring O-methyl group in phenolics denatured the AR activity. Finger millet seed coat polyphenols (SCP) has been found to inhibit AR reversibly by non-competitive inhibition. Results thus, provide a stronger evidence for the potentials of FMP in inhibiting cataractogenesis in humans.
|
Antioxidant activity assessed as DPPH radical scavenging activity after 20 mins
|
None
|
26.9
ug.mL-1
|
|
Journal : Bioorg. Med. Chem.
Title : Inhibition of aldose reductase from cataracted eye lenses by finger millet (Eleusine coracana) polyphenols.
Year : 2008
Volume : 16
Issue : 23
First Page : 10085
Last Page : 10090
Authors : Chethan S, Dharmesh SM, Malleshi NG.
Abstract : Retinopathy is a major cause of blindness in the Western world, while cataract is one of the three major causes of blindness worldwide. Diabetes is one of the major risk factor in retinopathy and cataract. The prevalence of blindness in India is 15 per 1000 while cataract alone accounts for 80% of this blindness. Diabetes induced cataract is characterized by an accumulation of sorbitol which is mediated by the action of a key enzyme aldose reductase (AR). Non-enzymatic glycation (binding of glucose to protein molecule) induced during diabetes appear to be the key factor for AR mediated sugar-induced cataract. Finger millet polyphenols (FMP) being a major anti-diabetic and antioxidant component, we have evaluated them for AR inhibiting activity. Phenolic constituents in FMP such as gallic, protocatechuic, p-hydroxy benzoic, p-coumaric, vanillic, syringic, ferulic, trans-cinnamic acids and the quercetin inhibited cataract eye lens effectively, the latter was more potent with an IC(50) of 14.8nM. Structure function analysis revealed that phenolics with OH group at 4th position was important for aldose reductase inhibitory property. Also the presence of neighboring O-methyl group in phenolics denatured the AR activity. Finger millet seed coat polyphenols (SCP) has been found to inhibit AR reversibly by non-competitive inhibition. Results thus, provide a stronger evidence for the potentials of FMP in inhibiting cataractogenesis in humans.
|
Antioxidant activity assessed as DPPH radical scavenging activity after 20 mins by UV-visible spectrophotometry
|
None
|
1.2
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.
|
Antioxidant activity assessed as DPPH free radical scavenging activity
|
None
|
5.0
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Antioxidant flavonoid glycosides from Daphniphyllum calycinum.
Year : 1998
Volume : 61
Issue : 5
First Page : 706
Last Page : 708
Authors : Gamez EJ, Luyengi L, Lee SK, Zhu LF, Zhou BN, Fong HH, Pezzuto JM, Kinghorn AD.
Abstract : A novel flavonoid diglycoside, 5,6,7,4'-tetrahydroxyflavonol 3-O-rutinoside (1), and a previously known compound, kaempferol 3-O-neohesperidoside (2), were isolated from an ethyl acetate extract of Daphniphyllum calycinum leaves that showed significant activity in a 1,1-diphenyl-2-picrylhydrazyl (DPPH) free-radical assay. The structure of 1 was elucidated by a combination of spectroscopic methods, and compounds 1 and 2 were found to be moderately active as antioxidants in the DPPH assay.
|
Antiinflammatory activity in human neutrophils assessed as respiratory burst inhibition at 1000 ug/ml by WST-1 assay
|
Homo sapiens
|
42.9
%
|
|
Journal : J. Nat. Prod.
Title : Inhibitory effect of macabarterin, a polyoxygenated ellagitannin from Macaranga barteri, on human neutrophil respiratory burst activity.
Year : 2008
Volume : 71
Issue : 11
First Page : 1906
Last Page : 1910
Authors : Ngoumfo RM, Ngounou GE, Tchamadeu CV, Qadir MI, Mbazoa CD, Begum A, Ngninzeko FN, Lontsi D, Choudhary MI.
Abstract : An ellagitannin with a 2,4-acyl group, named macabarterin (1), and a new ellagic acid glycoside, 3-O-methylellagic acid 4-O-β-d-xylopyranoside (2), were isolated from the stem bark extract of Macaranga barteri along with five known phenolic compounds, ellagic acid (3), 3-O-methylellagic acid (4), gallic acid (5), methyl gallate (6), and scopoletin (7). The structures of 1 and 2, as well as those of the known compounds, were elucidated on the basis of spectroscopic data and by comparison with reported data. Compounds 1-5 and 7 were tested for their anti-inflammatory potential in a cell-based respiratory burst assay, compound 1 being found an inhibitor of the superoxides produced in the cellular system.
|
Induction of toxin TSST-1 production in Staphylococcus aureus MN8 at 0.50 % after 24 hrs relative to control
|
Staphylococcus aureus
|
8.7
%
|
|
Journal : Antimicrob. Agents Chemother.
Title : Surfactants, aromatic and isoprenoid compounds, and fatty acid biosynthesis inhibitors suppress Staphylococcus aureus production of toxic shock syndrome toxin 1.
Year : 2009
Volume : 53
Issue : 5
First Page : 1898
Last Page : 1906
Authors : McNamara PJ, Syverson RE, Milligan-Myhre K, Frolova O, Schroeder S, Kidder J, Hoang T, Proctor RA.
Abstract : Menstrual toxic shock syndrome is a rare but potentially life-threatening illness manifest through the actions of Staphylococcus aureus toxic shock syndrome toxin 1 (TSST-1). Previous studies have shown that tampon additives can influence staphylococcal TSST-1 production. We report here on the TSST-1-suppressing activity of 34 compounds that are commonly used additives in the pharmaceutical, food, and perfume industries. Many of the tested chemicals had a minimal impact on the growth of S. aureus and yet were potent inhibitors of TSST-1 production. The TSST-1-reducing compounds included surfactants with an ether, amide, or amine linkage to their fatty acid moiety (e.g., myreth-3-myristate, Laureth-3, disodium lauroamphodiacetate, disodium lauramido monoethanolamido, sodium lauriminodipropionic acid, and triethanolamine laureth sulfate); aromatic compounds (e.g. phenylethyl and benzyl alcohols); and several isoprenoids and related compounds (e.g., terpineol and menthol). The membrane-targeting and -altering effects of the TSST-1-suppressing compounds led us to assess the activity of molecules that are known to inhibit fatty acid biosynthesis (e.g., cerulenin, triclosan, and hexachlorophene). These compounds also reduced S. aureus TSST-1 production. This study suggests that more additives than previously recognized inhibit the production of TSST-1.
|
Induction of toxin TSST-1 production in Staphylococcus aureus MN8 at 0.10 % after 24 hrs relative to control
|
Staphylococcus aureus
|
41.4
%
|
|
Journal : Antimicrob. Agents Chemother.
Title : Surfactants, aromatic and isoprenoid compounds, and fatty acid biosynthesis inhibitors suppress Staphylococcus aureus production of toxic shock syndrome toxin 1.
Year : 2009
Volume : 53
Issue : 5
First Page : 1898
Last Page : 1906
Authors : McNamara PJ, Syverson RE, Milligan-Myhre K, Frolova O, Schroeder S, Kidder J, Hoang T, Proctor RA.
Abstract : Menstrual toxic shock syndrome is a rare but potentially life-threatening illness manifest through the actions of Staphylococcus aureus toxic shock syndrome toxin 1 (TSST-1). Previous studies have shown that tampon additives can influence staphylococcal TSST-1 production. We report here on the TSST-1-suppressing activity of 34 compounds that are commonly used additives in the pharmaceutical, food, and perfume industries. Many of the tested chemicals had a minimal impact on the growth of S. aureus and yet were potent inhibitors of TSST-1 production. The TSST-1-reducing compounds included surfactants with an ether, amide, or amine linkage to their fatty acid moiety (e.g., myreth-3-myristate, Laureth-3, disodium lauroamphodiacetate, disodium lauramido monoethanolamido, sodium lauriminodipropionic acid, and triethanolamine laureth sulfate); aromatic compounds (e.g. phenylethyl and benzyl alcohols); and several isoprenoids and related compounds (e.g., terpineol and menthol). The membrane-targeting and -altering effects of the TSST-1-suppressing compounds led us to assess the activity of molecules that are known to inhibit fatty acid biosynthesis (e.g., cerulenin, triclosan, and hexachlorophene). These compounds also reduced S. aureus TSST-1 production. This study suggests that more additives than previously recognized inhibit the production of TSST-1.
|
Antioxidant activity assessed as DPPH radical scavenging activity after 30 mins by spectrophotometric analysisic analysis
|
None
|
1.85
ug.mL-1
|
|
Journal : Bioorg. Med. Chem.
Title : Tylosema esculentum extractives and their bioactivity.
Year : 2011
Volume : 19
Issue : 17
First Page : 5225
Last Page : 5230
Authors : Mazimba O, Majinda RR, Modibedi C, Masesane IB, Cencič A, Chingwaru W.
Abstract : The investigation of Tylosema esculentum (Morama) husks, cotyledons, and tuber yielded griffonilide 2, compound 1, griffonin 3, gallic acid 4, protocatechuic acid 5, β-sitosterol 6, behenic acid 7, oleic acid 8, sucrose 9, 2-O-ethyl-α-D-glucopyranoside 10, kaempferol 11 and kaempferol-3-O-β-D-glucopyranoside 12. The structures of the isolates were determined by NMR, HR-TOF EIMS, IR and UV-vis spectroscopy, and by comparison with literature data. The husk EtOAc and n-butanol extracts demonstrated >90% DPPH radical scavenging activity at concentrations of 25, 50 and 250 μg/mL. Furthermore the husk extracts showed higher total phenolic content (233 mg GAE/g). The extractives exhibited minimum inhibitory quantities of 50-100 μg or no activity against Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa and Candida albicans. The tuber extracts were inactive against Caco-2 and Hela cell lines, while the husk extracts showed low activity against Caco-2 and Vero cell line with IC(50) values >400 μg/mL. The GC-MS analysis showed the beans and tuber non-polar (n-hexane) extracts major constituents as fatty acids.
|
Antioxidant activity assessed as DPPH free radical scavenging activity
|
None
|
3.8
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.
|
Antioxidant activity assessed as superoxide dismutase-like activity by SOD-WST assay
|
None
|
6.3
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Diarylheptanoid sulfates and related compounds from Myrica rubra bark.
Year : 2012
Volume : 75
Issue : 10
First Page : 1798
Last Page : 1802
Authors : Yoshimura M, Yamakami S, Amakura Y, Yoshida T.
Abstract : Three new diarylheptanoids, myricanol 11-sulfate (1), juglanin B 11-sulfate (2), and myricanone 5-O-(6'-O-galloyl)glucoside (3), were isolated from the bark of Myrica rubra. Compounds 1 and 2 were characterized as diarylheptanoid sulfates on the basis of spectroscopic analyses. The antioxidative activities of the fractionated extracts and isolated compounds were estimated by the oxygen radical absorbance capacity (ORAC) and superoxide dismutase (SOD)-like activity assays. The major isolate, myricitrin (4), displayed a high ORAC value and moderate SOD-like activity (13,198 μmol TE (Trolox equivalent)/g and IC₅₀ 127.5 μg/mL, respectively), which might explain the potent antioxidative activity of this material.
|
Inhibition of porcine pancreatic lipase using micellar solution of triolein as substrate at 1 mM preincubated for 5 mins before substrate addition measured after 30 mins
|
Sus scrofa
|
4.0
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Substrate-like water soluble lipase inhibitors from Filipendula kamtschatica.
Year : 2012
Volume : 22
Issue : 20
First Page : 6410
Last Page : 6412
Authors : Kato E, Yama M, Nakagomi R, Shibata T, Hosokawa K, Kawabata J.
Abstract : Filipendula kamtschatica is a plant utilized as a traditional medicine by Ainu people in Japan, but its chemical constituents are not much studied. Pancreatic lipase inhibitors are a promising tool for the treatment of obesity. We searched for natural lipase inhibitors from F. kamtschatica and two new compounds were isolated along with the known flavonoid glycoside. The structure elucidation of new compounds revealed these two to be 2-O-caffeoyl-4-O-galloyl-L-threonic acid and 3-O-caffeoyl-4-O-galloyl-L-threonic acid, which can be recognized as a pancreatic lipase's substrate-like structure. The isolated compounds all showed an inhibitory activity against porcine pancreatic lipase and one of the isomer, 3-O-caffeoyl-4-O-galloyl-L-threonic acid, possessed the most potent activity with IC(50) value showing an order lower value compared to others. The substrate-like structure of the new compounds seemed to be important for their activity.
|
Inhibition of mushroom tyrosinase using L-DOPA as substrate at 100 ug/ml after 10 mins
|
Agaricus bisporus
|
31.7
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Design, synthesis and molecular simulation studies of dihydrostilbene derivatives as potent tyrosinase inhibitors.
Year : 2012
Volume : 22
Issue : 17
First Page : 5523
Last Page : 5526
Authors : Vontzalidou A, Zoidis G, Chaita E, Makropoulou M, Aligiannis N, Lambrinidis G, Mikros E, Skaltsounis AL.
Abstract : The synthesis, molecular modeling and biological evaluation of substituted deoxybenzoins and optimized dihydrostilbenes are reported. Preliminary structure-activity relationship data were elucidated and lead compounds suitable for further optimization were discovered. Dihydrostilbene 7 is a particularly potent inhibitor (IC(50)=8.44 μM, more potent than kojic acid).
|
Antioxidant activity assessed as DPPH scavenging activity after 2 hr by spectrophotometry
|
None
|
2.06
ug.mL-1
|
|
Journal : Med Chem Res
Title : 3,4-Dihydropyrimidin-2(1H)-one derivatives: Organocatalysed microwave assisted synthesis and evaluation of their antioxidant activity
Year : 2012
Volume : 21
Issue : 12
First Page : 4506
Last Page : 4511
Authors : Gangwar N, Kasana VK
|
Antioxidant activity in phosphate buffer at pH 6.6 assessed as reducing power measuring conversion of potassium ferricyanide to ferrous form after 10 min by spectrophotometry
|
None
|
5.25
ug.mL-1
|
|
Journal : Med Chem Res
Title : 3,4-Dihydropyrimidin-2(1H)-one derivatives: Organocatalysed microwave assisted synthesis and evaluation of their antioxidant activity
Year : 2012
Volume : 21
Issue : 12
First Page : 4506
Last Page : 4511
Authors : Gangwar N, Kasana VK
|
Antioxidant activity assessed as DPPH free radical scavenging activity after 20 min by UV-Vis spectrophotometric analysis
|
None
|
1.28
ug.mL-1
|
|
Journal : Eur. J. Med. Chem.
Title : Microwave synthesis, characterization and bio-efficacy evaluation of novel chalcone based 6-carbethoxy-2-cyclohexen-1-one and 2H-indazol-3-ol derivatives.
Year : 2013
Volume : 59
First Page : 120
Last Page : 131
Authors : Shakil NA, Singh MK, Sathiyendiran M, Kumar J, Padaria JC.
Abstract : Novel chalcone based 6-carbethoxy-2-cyclohexen-1-one and 2H-indazol-3-ol derivatives were synthesized and characterized by using spectral techniques like IR, (1)H NMR, (13)C NMR, COSY, DEPT, and GC-MS. All these compounds were screened for anti-fungal, anti-bacterial and anti-oxidant activity. Cyclohexenone derivatives, in general, showed better anti-fungal and anti-bacterial activity than parent chalcones. Whereas, all the Indazole derivatives showed very good anti-oxidant activity and some were also found to be active as anti-bacterial agent. Among the screened compounds, 15 was found to be most active as anti-fungal agent (against Rhizoctonia solani, LC(50) = 2.36 μg mL(-1)), 15b was found to be most active anti-bacterial agent (against Klebsiella pneumonia, MIC = 24.68 μg mL(-1)) and 14b emerged as most active anti-oxidant (IC(50) = 19.81 μg mL(-1)).
|
Antioxidant activity assessed as inhibition of DPPH free radicals at 400 uM after 30 min by microplate reader analysis relative to control
|
None
|
77.68
%
|
|
Journal : Med Chem Res
Title : Synthesis, structure, anticancer, and antioxidant activity of para-xylyl linked bis-benzimidazolium salts and respective dinuclear Ag(I) N-heterocyclic carbene complexes (Part-II)
Year : 2013
Volume : 22
Issue : 10
First Page : 4663
Last Page : 4676
Authors : Haque RA, Iqbal MA, Asekunowo P, Majid AMSA, Khadeer Ahamed MB, Umar MI, Al-Rawi SS, Al-Suede FSR
|
Antioxidant activity assessed as DPPH radical scavenging activity
|
None
|
6.0
%
|
|
Journal : Bioorg. Med. Chem.
Title : N-(Phenoxyalkyl)amides as MT(1) and MT(2) ligands: antioxidant properties and inhibition of Ca(2+)/CaM-dependent kinase II.
Year : 2013
Volume : 21
Issue : 4
First Page : 847
Last Page : 851
Authors : Carocci A, Catalano A, Bruno C, Lovece A, Roselli MG, Cavalluzzi MM, De Santis F, De Palma A, Rusciano MR, Illario M, Franchini C, Lentini G.
Abstract : Recently a series of chiral N-(phenoxyalkyl)amides have been reported as potent MT(1) and MT(2) melatonergic ligands. Some of these compounds were selected and tested for their antioxidant properties by measuring their reducing effect against oxidation of 2',7'-dichlorodihydrofluorescein (DCFH) in the DCFH-diacetate (DCFH-DA) assay. Among the tested compounds, N-[2-(3-methoxyphenoxy)propyl]butanamide displayed potent antioxidant activity that was stereoselective, the (R)-enantiomer performing as the eutomer. This compound displayed strong cytoprotective activity against H(2)O(2)-induced cytotoxicity resulting slightly more active than melatonin, and performed as Ca(2+)/calmodulin-dependent kinase II (CaMKII) inhibitor, too.
|
Antioxidant activity assessed as DPPH radical scavenging activity at 0.1 mM
|
Hepatitis GB virus B
|
97.14
%
|
|
Journal : Bioorg. Med. Chem.
Title : N-(Phenoxyalkyl)amides as MT(1) and MT(2) ligands: antioxidant properties and inhibition of Ca(2+)/CaM-dependent kinase II.
Year : 2013
Volume : 21
Issue : 4
First Page : 847
Last Page : 851
Authors : Carocci A, Catalano A, Bruno C, Lovece A, Roselli MG, Cavalluzzi MM, De Santis F, De Palma A, Rusciano MR, Illario M, Franchini C, Lentini G.
Abstract : Recently a series of chiral N-(phenoxyalkyl)amides have been reported as potent MT(1) and MT(2) melatonergic ligands. Some of these compounds were selected and tested for their antioxidant properties by measuring their reducing effect against oxidation of 2',7'-dichlorodihydrofluorescein (DCFH) in the DCFH-diacetate (DCFH-DA) assay. Among the tested compounds, N-[2-(3-methoxyphenoxy)propyl]butanamide displayed potent antioxidant activity that was stereoselective, the (R)-enantiomer performing as the eutomer. This compound displayed strong cytoprotective activity against H(2)O(2)-induced cytotoxicity resulting slightly more active than melatonin, and performed as Ca(2+)/calmodulin-dependent kinase II (CaMKII) inhibitor, too.
|
Inhibition of ADAM17 alpha-secretase activity in human UI87 cells using amyloid beta precursor protein as substrate at 40 ug/ml after 24 hrs by fluorimetric analysis
|
Homo sapiens
|
38.9
%
|
|
Journal : Eur. J. Med. Chem.
Title : Alkyl esters of gallic acid as anticancer agents: a review.
Year : 2013
Volume : 60
First Page : 233
Last Page : 239
Authors : Locatelli C, Filippin-Monteiro FB, Filippin-Monteiro FB, Creczynski-Pasa TB.
Abstract : The current review presents the antitumoral properties of gallic acid and its ester derivatives. Numerous studies have indicated that the alkyl esters are more effective against tumor cell lines than gallic acid, and that this activity is related to their hydrophobic moiety. All related studies have shown that the antitumor activity is interconnected to the induction of apoptosis by different mechanisms and it depends on the cell type. The results presented in this review may help to emphasize that these compounds could be promising as a new alternative for the treatment of cancer, either alone or in combination with other antitumor drugs to potentiate their effects.
|
Inhibition of ADAM17 alpha-secretase activity in human UI87 cells using amyloid beta precursor protein as substrate at 30 ug/ml after 24 hrs by fluorimetric analysis
|
Homo sapiens
|
43.5
%
|
|
Journal : Eur. J. Med. Chem.
Title : Alkyl esters of gallic acid as anticancer agents: a review.
Year : 2013
Volume : 60
First Page : 233
Last Page : 239
Authors : Locatelli C, Filippin-Monteiro FB, Filippin-Monteiro FB, Creczynski-Pasa TB.
Abstract : The current review presents the antitumoral properties of gallic acid and its ester derivatives. Numerous studies have indicated that the alkyl esters are more effective against tumor cell lines than gallic acid, and that this activity is related to their hydrophobic moiety. All related studies have shown that the antitumor activity is interconnected to the induction of apoptosis by different mechanisms and it depends on the cell type. The results presented in this review may help to emphasize that these compounds could be promising as a new alternative for the treatment of cancer, either alone or in combination with other antitumor drugs to potentiate their effects.
|
Inhibition of ADAM17 alpha-secretase activity in human UI87 cells using amyloid beta precursor protein as substrate at 20 ug/ml after 24 hrs by fluorimetric analysis
|
Homo sapiens
|
47.9
%
|
|
Journal : Eur. J. Med. Chem.
Title : Alkyl esters of gallic acid as anticancer agents: a review.
Year : 2013
Volume : 60
First Page : 233
Last Page : 239
Authors : Locatelli C, Filippin-Monteiro FB, Filippin-Monteiro FB, Creczynski-Pasa TB.
Abstract : The current review presents the antitumoral properties of gallic acid and its ester derivatives. Numerous studies have indicated that the alkyl esters are more effective against tumor cell lines than gallic acid, and that this activity is related to their hydrophobic moiety. All related studies have shown that the antitumor activity is interconnected to the induction of apoptosis by different mechanisms and it depends on the cell type. The results presented in this review may help to emphasize that these compounds could be promising as a new alternative for the treatment of cancer, either alone or in combination with other antitumor drugs to potentiate their effects.
|
Cytotoxicity against rat fibroblast cells
|
Rattus norvegicus
|
20.0
ug.mL-1
|
|
Journal : Eur. J. Med. Chem.
Title : Alkyl esters of gallic acid as anticancer agents: a review.
Year : 2013
Volume : 60
First Page : 233
Last Page : 239
Authors : Locatelli C, Filippin-Monteiro FB, Filippin-Monteiro FB, Creczynski-Pasa TB.
Abstract : The current review presents the antitumoral properties of gallic acid and its ester derivatives. Numerous studies have indicated that the alkyl esters are more effective against tumor cell lines than gallic acid, and that this activity is related to their hydrophobic moiety. All related studies have shown that the antitumor activity is interconnected to the induction of apoptosis by different mechanisms and it depends on the cell type. The results presented in this review may help to emphasize that these compounds could be promising as a new alternative for the treatment of cancer, either alone or in combination with other antitumor drugs to potentiate their effects.
|
Cytotoxicity against rat epithelial cells
|
Rattus norvegicus
|
20.0
ug.mL-1
|
|
Journal : Eur. J. Med. Chem.
Title : Alkyl esters of gallic acid as anticancer agents: a review.
Year : 2013
Volume : 60
First Page : 233
Last Page : 239
Authors : Locatelli C, Filippin-Monteiro FB, Filippin-Monteiro FB, Creczynski-Pasa TB.
Abstract : The current review presents the antitumoral properties of gallic acid and its ester derivatives. Numerous studies have indicated that the alkyl esters are more effective against tumor cell lines than gallic acid, and that this activity is related to their hydrophobic moiety. All related studies have shown that the antitumor activity is interconnected to the induction of apoptosis by different mechanisms and it depends on the cell type. The results presented in this review may help to emphasize that these compounds could be promising as a new alternative for the treatment of cancer, either alone or in combination with other antitumor drugs to potentiate their effects.
|
Cytotoxicity against human KB cells
|
Homo sapiens
|
13.2
ug.mL-1
|
|
Journal : Eur. J. Med. Chem.
Title : Alkyl esters of gallic acid as anticancer agents: a review.
Year : 2013
Volume : 60
First Page : 233
Last Page : 239
Authors : Locatelli C, Filippin-Monteiro FB, Filippin-Monteiro FB, Creczynski-Pasa TB.
Abstract : The current review presents the antitumoral properties of gallic acid and its ester derivatives. Numerous studies have indicated that the alkyl esters are more effective against tumor cell lines than gallic acid, and that this activity is related to their hydrophobic moiety. All related studies have shown that the antitumor activity is interconnected to the induction of apoptosis by different mechanisms and it depends on the cell type. The results presented in this review may help to emphasize that these compounds could be promising as a new alternative for the treatment of cancer, either alone or in combination with other antitumor drugs to potentiate their effects.
|
Antioxidant activity assessed as inhibition of ABTS free radical generation at 9 uM after 20 mins by UV spectrophotometric analysis relative to control
|
None
|
61.6
%
|
|
Journal : Bioorg. Med. Chem.
Title : Indole derivatives as dual-effective agents for the treatment of neurodegenerative diseases: synthesis, biological evaluation, and molecular modeling studies.
Year : 2013
Volume : 21
Issue : 15
First Page : 4575
Last Page : 4580
Authors : Buemi MR, De Luca L, Chimirri A, Ferro S, Gitto R, Alvarez-Builla J, Alajarin R.
Abstract : Several indole derivatives, that were highly potent ligands of GluN2B-subunit-containing N-methyl-D-aspartate (NMDA) receptor, also demonstrated antioxidant properties in ABTS method. In particular, the 2-(4-benzylpiperidin-1-yl)-1-(5-hydroxy-1H-indol-3-yl)ethanone (1) proved to be a dual-effective neuroprotective agent. With the aim to increase the antioxidant properties we added a catechol moiety onto piperidine moiety. The designed hybrid derivative 3,4-dihydroxy-N-[1-[2-(5-hydroxy-1H-indol-3-yl)-2-oxoethyl]piperidin-4-yl]benzamide (10) was the most effective antioxidant agent (>94.1 ± 0.1% of inhibition at 17 μM) and showed GluN2B/NMDA receptor affinity at low micromolar concentration (IC₅₀ 0.66 μM). By means of computational studies we explored the effect of the presence of this antioxidant fragment during the recognition process to binding pocket.
|
Antioxidant activity assessed as inhibition of ABTS free radical generation at 17 uM after 20 mins by UV spectrophotometric analysis relative to control
|
None
|
94.1
%
|
|
Journal : Bioorg. Med. Chem.
Title : Indole derivatives as dual-effective agents for the treatment of neurodegenerative diseases: synthesis, biological evaluation, and molecular modeling studies.
Year : 2013
Volume : 21
Issue : 15
First Page : 4575
Last Page : 4580
Authors : Buemi MR, De Luca L, Chimirri A, Ferro S, Gitto R, Alvarez-Builla J, Alajarin R.
Abstract : Several indole derivatives, that were highly potent ligands of GluN2B-subunit-containing N-methyl-D-aspartate (NMDA) receptor, also demonstrated antioxidant properties in ABTS method. In particular, the 2-(4-benzylpiperidin-1-yl)-1-(5-hydroxy-1H-indol-3-yl)ethanone (1) proved to be a dual-effective neuroprotective agent. With the aim to increase the antioxidant properties we added a catechol moiety onto piperidine moiety. The designed hybrid derivative 3,4-dihydroxy-N-[1-[2-(5-hydroxy-1H-indol-3-yl)-2-oxoethyl]piperidin-4-yl]benzamide (10) was the most effective antioxidant agent (>94.1 ± 0.1% of inhibition at 17 μM) and showed GluN2B/NMDA receptor affinity at low micromolar concentration (IC₅₀ 0.66 μM). By means of computational studies we explored the effect of the presence of this antioxidant fragment during the recognition process to binding pocket.
|
Inhibition of sodium fluorescein uptake in OATP1B1-transfected CHO cells at an equimolar substrate-inhibitor concentration of 10 uM
|
Cricetulus griseus
|
67.94
%
|
|
Journal : Mol. Pharmacol.
Title : Structure-based identification of OATP1B1/3 inhibitors.
Year : 2013
Volume : 83
Issue : 6
First Page : 1257
Last Page : 1267
Authors : De Bruyn T, van Westen GJ, Ijzerman AP, Stieger B, de Witte P, Augustijns PF, Annaert PP.
Abstract : Several recent studies show that inhibition of the hepatic transport proteins organic anion-transporting polypeptide 1B1 (OATP1B1) and 1B3 (OATP1B3) can result in clinically relevant drug-drug interactions (DDI). To avoid late-stage development drug failures due to OATP1B-mediated DDI, predictive in vitro and in silico methods should be implemented at an early stage of the drug candidate evaluation process. In the present study, we first developed a high-throughput in vitro transporter inhibition assay for the OATP1B subfamily. A total of 2000 compounds were tested as potential modulators of the uptake of the OATP1B substrate sodium fluorescein, in OATP1B1- or 1B3-transfected Chinese hamster ovary cells. At an equimolar substrate-inhibitor concentration of 10 µM, 212 and 139 molecules were identified as OATP1B1 and OATP1B3 inhibitors, respectively (minimum 50% inhibition). For 69 compounds, previously not identified as OATP1B inhibitors, concentration-dependent inhibition was also determined, yielding Ki values ranging from 0.06 to 6.5 µM. Based on these in vitro data, we subsequently developed a proteochemometrics-based in silico model, which predicted OATP1B inhibitors in the test group (20% of the dataset) with high specificity (86%) and sensitivity (78%). Moreover, several physicochemical compound properties and substructures related to OATP1B1/1B3 inhibition or inactivity were identified. Finally, model performance was prospectively verified with a set of 54 compounds not included in the original dataset. This validation indicated that 80 and 74% of the compounds were correctly classified for OATP1B1 and OATP1B3 inhibition, respectively.
|
Inhibition of sodium fluorescein uptake in OATP1B3-transfected CHO cells at an equimolar substrate-inhibitor concentration of 10 uM
|
Cricetulus griseus
|
91.35
%
|
|
Journal : Mol. Pharmacol.
Title : Structure-based identification of OATP1B1/3 inhibitors.
Year : 2013
Volume : 83
Issue : 6
First Page : 1257
Last Page : 1267
Authors : De Bruyn T, van Westen GJ, Ijzerman AP, Stieger B, de Witte P, Augustijns PF, Annaert PP.
Abstract : Several recent studies show that inhibition of the hepatic transport proteins organic anion-transporting polypeptide 1B1 (OATP1B1) and 1B3 (OATP1B3) can result in clinically relevant drug-drug interactions (DDI). To avoid late-stage development drug failures due to OATP1B-mediated DDI, predictive in vitro and in silico methods should be implemented at an early stage of the drug candidate evaluation process. In the present study, we first developed a high-throughput in vitro transporter inhibition assay for the OATP1B subfamily. A total of 2000 compounds were tested as potential modulators of the uptake of the OATP1B substrate sodium fluorescein, in OATP1B1- or 1B3-transfected Chinese hamster ovary cells. At an equimolar substrate-inhibitor concentration of 10 µM, 212 and 139 molecules were identified as OATP1B1 and OATP1B3 inhibitors, respectively (minimum 50% inhibition). For 69 compounds, previously not identified as OATP1B inhibitors, concentration-dependent inhibition was also determined, yielding Ki values ranging from 0.06 to 6.5 µM. Based on these in vitro data, we subsequently developed a proteochemometrics-based in silico model, which predicted OATP1B inhibitors in the test group (20% of the dataset) with high specificity (86%) and sensitivity (78%). Moreover, several physicochemical compound properties and substructures related to OATP1B1/1B3 inhibition or inactivity were identified. Finally, model performance was prospectively verified with a set of 54 compounds not included in the original dataset. This validation indicated that 80 and 74% of the compounds were correctly classified for OATP1B1 and OATP1B3 inhibition, respectively.
|
Inhibition of reduced carboxymethylated-kappa-casein (unknown origin) conversion to amyloid fibrils at 1:0.1 protein to compound molar ratio after 1000 mins by thioflavin T fluorescence assay relative to control
|
Homo sapiens
|
3.0
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Gallic acid is the major component of grape seed extract that inhibits amyloid fibril formation.
Year : 2013
Volume : 23
Issue : 23
First Page : 6336
Last Page : 6340
Authors : Liu Y, Pukala TL, Musgrave IF, Williams DM, Dehle FC, Carver JA.
Abstract : Many protein misfolding diseases, for example, Alzheimer's, Parkinson's and Huntington's, are characterised by the accumulation of protein aggregates in an amyloid fibrillar form. Natural products which inhibit fibril formation are a promising avenue to explore as therapeutics for the treatment of these diseases. In this study we have shown, using in vitro thioflavin T assays and transmission electron microscopy, that grape seed extract inhibits fibril formation of kappa-casein (κ-CN), a milk protein which forms amyloid fibrils spontaneously under physiological conditions. Among the components of grape seed extract, gallic acid was the most active component at inhibiting κ-CN fibril formation, by stabilizing κ-CN to prevent its aggregation. Concomitantly, gallic acid significantly reduced the toxicity of κ-CN to pheochromocytoma12 cells. Furthermore, gallic acid effectively inhibited fibril formation by the amyloid-beta peptide, the putative causative agent in Alzheimer's disease. It is concluded that the gallate moiety has the fibril-inhibitory activity.
|
Inhibition of reduced carboxymethylated-kappa-casein (unknown origin) conversion to amyloid fibrils at 1:0.5 protein to compound molar ratio after 1000 mins by thioflavin T fluorescence assay relative to control
|
Homo sapiens
|
54.0
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Gallic acid is the major component of grape seed extract that inhibits amyloid fibril formation.
Year : 2013
Volume : 23
Issue : 23
First Page : 6336
Last Page : 6340
Authors : Liu Y, Pukala TL, Musgrave IF, Williams DM, Dehle FC, Carver JA.
Abstract : Many protein misfolding diseases, for example, Alzheimer's, Parkinson's and Huntington's, are characterised by the accumulation of protein aggregates in an amyloid fibrillar form. Natural products which inhibit fibril formation are a promising avenue to explore as therapeutics for the treatment of these diseases. In this study we have shown, using in vitro thioflavin T assays and transmission electron microscopy, that grape seed extract inhibits fibril formation of kappa-casein (κ-CN), a milk protein which forms amyloid fibrils spontaneously under physiological conditions. Among the components of grape seed extract, gallic acid was the most active component at inhibiting κ-CN fibril formation, by stabilizing κ-CN to prevent its aggregation. Concomitantly, gallic acid significantly reduced the toxicity of κ-CN to pheochromocytoma12 cells. Furthermore, gallic acid effectively inhibited fibril formation by the amyloid-beta peptide, the putative causative agent in Alzheimer's disease. It is concluded that the gallate moiety has the fibril-inhibitory activity.
|
Inhibition of reduced carboxymethylated-kappa-casein (unknown origin) conversion to amyloid fibrils at 1:1 protein to compound molar ratio after 1000 mins by thioflavin T fluorescence assay relative to control
|
Homo sapiens
|
87.0
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Gallic acid is the major component of grape seed extract that inhibits amyloid fibril formation.
Year : 2013
Volume : 23
Issue : 23
First Page : 6336
Last Page : 6340
Authors : Liu Y, Pukala TL, Musgrave IF, Williams DM, Dehle FC, Carver JA.
Abstract : Many protein misfolding diseases, for example, Alzheimer's, Parkinson's and Huntington's, are characterised by the accumulation of protein aggregates in an amyloid fibrillar form. Natural products which inhibit fibril formation are a promising avenue to explore as therapeutics for the treatment of these diseases. In this study we have shown, using in vitro thioflavin T assays and transmission electron microscopy, that grape seed extract inhibits fibril formation of kappa-casein (κ-CN), a milk protein which forms amyloid fibrils spontaneously under physiological conditions. Among the components of grape seed extract, gallic acid was the most active component at inhibiting κ-CN fibril formation, by stabilizing κ-CN to prevent its aggregation. Concomitantly, gallic acid significantly reduced the toxicity of κ-CN to pheochromocytoma12 cells. Furthermore, gallic acid effectively inhibited fibril formation by the amyloid-beta peptide, the putative causative agent in Alzheimer's disease. It is concluded that the gallate moiety has the fibril-inhibitory activity.
|
Inhibition of reduced carboxymethylated-kappa-casein (unknown origin) conversion to amyloid fibrils at 1:2 protein to compound molar ratio after 1000 mins by thioflavin T fluorescence assay relative to control
|
Homo sapiens
|
98.0
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Gallic acid is the major component of grape seed extract that inhibits amyloid fibril formation.
Year : 2013
Volume : 23
Issue : 23
First Page : 6336
Last Page : 6340
Authors : Liu Y, Pukala TL, Musgrave IF, Williams DM, Dehle FC, Carver JA.
Abstract : Many protein misfolding diseases, for example, Alzheimer's, Parkinson's and Huntington's, are characterised by the accumulation of protein aggregates in an amyloid fibrillar form. Natural products which inhibit fibril formation are a promising avenue to explore as therapeutics for the treatment of these diseases. In this study we have shown, using in vitro thioflavin T assays and transmission electron microscopy, that grape seed extract inhibits fibril formation of kappa-casein (κ-CN), a milk protein which forms amyloid fibrils spontaneously under physiological conditions. Among the components of grape seed extract, gallic acid was the most active component at inhibiting κ-CN fibril formation, by stabilizing κ-CN to prevent its aggregation. Concomitantly, gallic acid significantly reduced the toxicity of κ-CN to pheochromocytoma12 cells. Furthermore, gallic acid effectively inhibited fibril formation by the amyloid-beta peptide, the putative causative agent in Alzheimer's disease. It is concluded that the gallate moiety has the fibril-inhibitory activity.
|
Antioxidant activity of the compound assessed as inhibition of ABTS radicals at 9 uM after 20 mins by spectrophotometric analysis
|
None
|
61.6
%
|
|
Journal : Bioorg. Med. Chem.
Title : Synthesis, modelling and biological characterization of 3-substituted-1H-indoles as ligands of GluN2B-containing N-methyl-d-aspartate receptors.
Year : 2014
Volume : 22
Issue : 3
First Page : 1040
Last Page : 1048
Authors : Gitto R, De Luca L, Ferro S, Russo E, De Sarro G, Chisari M, Ciranna L, Alvarez-Builla J, Alajarin R, Buemi MR, Chimirri A.
Abstract : A three-step synthetic pathway has been employed to synthesize a small library of 2-(4-arylpiperidin-1-yl)-1-(1H-indol-3-yl)ethanone and 2-(4-arylpiperidin-1-yl)-1-(1H-indol-3-yl)ethane-1,2-dione derivatives that have been screened in [(3)H]ifenprodil competition binding assay. Some compounds exhibited significant binding affinity at nanomolar concentration, the most active being ligand 35 (IC50=5.5nM). Docking experiments suggested the main interactions between 35 and GluN2B-containing NMDA receptors. Notably, the compound 35 reduced NMDA-mediated excitatory post-synaptic currents recorded in mouse hippocampal slices indicating antagonistic effects (50nM). Moreover, the compound 35 has shown antioxidant effects in a preliminary screening, thus suggesting that it might be considered prototype for future drug development of novel 'dual target' neuroprotective agents.
|
Antioxidant activity of the compound assessed as inhibition of ABTS radicals at 17 uM after 20 mins by spectrophotometric analysis
|
None
|
94.1
%
|
|
Journal : Bioorg. Med. Chem.
Title : Synthesis, modelling and biological characterization of 3-substituted-1H-indoles as ligands of GluN2B-containing N-methyl-d-aspartate receptors.
Year : 2014
Volume : 22
Issue : 3
First Page : 1040
Last Page : 1048
Authors : Gitto R, De Luca L, Ferro S, Russo E, De Sarro G, Chisari M, Ciranna L, Alvarez-Builla J, Alajarin R, Buemi MR, Chimirri A.
Abstract : A three-step synthetic pathway has been employed to synthesize a small library of 2-(4-arylpiperidin-1-yl)-1-(1H-indol-3-yl)ethanone and 2-(4-arylpiperidin-1-yl)-1-(1H-indol-3-yl)ethane-1,2-dione derivatives that have been screened in [(3)H]ifenprodil competition binding assay. Some compounds exhibited significant binding affinity at nanomolar concentration, the most active being ligand 35 (IC50=5.5nM). Docking experiments suggested the main interactions between 35 and GluN2B-containing NMDA receptors. Notably, the compound 35 reduced NMDA-mediated excitatory post-synaptic currents recorded in mouse hippocampal slices indicating antagonistic effects (50nM). Moreover, the compound 35 has shown antioxidant effects in a preliminary screening, thus suggesting that it might be considered prototype for future drug development of novel 'dual target' neuroprotective agents.
|
Antioxidant activity of the compound assessed as inhibition of ABTS radicals at 33 uM after 20 mins by spectrophotometric analysis
|
None
|
93.9
%
|
|
Journal : Bioorg. Med. Chem.
Title : Synthesis, modelling and biological characterization of 3-substituted-1H-indoles as ligands of GluN2B-containing N-methyl-d-aspartate receptors.
Year : 2014
Volume : 22
Issue : 3
First Page : 1040
Last Page : 1048
Authors : Gitto R, De Luca L, Ferro S, Russo E, De Sarro G, Chisari M, Ciranna L, Alvarez-Builla J, Alajarin R, Buemi MR, Chimirri A.
Abstract : A three-step synthetic pathway has been employed to synthesize a small library of 2-(4-arylpiperidin-1-yl)-1-(1H-indol-3-yl)ethanone and 2-(4-arylpiperidin-1-yl)-1-(1H-indol-3-yl)ethane-1,2-dione derivatives that have been screened in [(3)H]ifenprodil competition binding assay. Some compounds exhibited significant binding affinity at nanomolar concentration, the most active being ligand 35 (IC50=5.5nM). Docking experiments suggested the main interactions between 35 and GluN2B-containing NMDA receptors. Notably, the compound 35 reduced NMDA-mediated excitatory post-synaptic currents recorded in mouse hippocampal slices indicating antagonistic effects (50nM). Moreover, the compound 35 has shown antioxidant effects in a preliminary screening, thus suggesting that it might be considered prototype for future drug development of novel 'dual target' neuroprotective agents.
|
Inhibition of Influenza A virus (A/RI/5+/1957(H2N2)) recombinant neuraminidase using MUNANA as substrate at 100 uM after 30 mins
|
Influenza A virus (A/RI/5+/1957(H2N2))
|
3.0
%
|
|
Journal : Bioorg. Med. Chem.
Title : Benzophenone C-glucosides and gallotannins from mango tree stem bark with broad-spectrum anti-viral activity.
Year : 2014
Volume : 22
Issue : 7
First Page : 2236
Last Page : 2243
Authors : Abdel-Mageed WM, Bayoumi SA, Chen C, Vavricka CJ, Li L, Malik A, Dai H, Song F, Wang L, Zhang J, Gao GF, Lv Y, Liu L, Liu X, Sayed HM, Zhang L.
Abstract : The high mutation rate of RNA viruses has resulted in limitation of vaccine effectiveness and increased emergence of drug-resistant viruses. New effective antivirals are therefore needed to control of the highly mutative RNA viruses. The n-butanol fraction of the stem bark of Mangifera indica exhibited inhibitory activity against influenza neuraminidase (NA) and coxsackie virus 3C protease. Bioassay guided phytochemical study of M. indica stem bark afforded two new compounds including one benzophenone C-glycoside (4) and one xanthone dimer (7), together with eleven known compounds. The structures of these isolated compounds were elucidated on the basis of spectroscopic evidences and correlated with known compounds. Anti-influenza and anti-coxsackie virus activities were evaluated by determining the inhibition of anti-influenza neuraminidase (NA) from pandemic A/RI/5+/1957 H2N2 influenza A virus and inhibition of coxsackie B3 virus 3C protease, respectively. The highest anti-influenza activity was observed for compounds 8 and 9 with IC50 values of 11.9 and 9.2μM, respectively. Compounds 8 and 9 were even more potent against coxsackie B3 virus 3C protease, with IC50 values of 1.1 and 2.0μM, respectively. Compounds 8 and 9 showed weak cytotoxic effect against human hepatocellular carcinoma and human epithelial carcinoma cell lines through MTT assay.
|
Antioxidant activity assessed as DPPH radical scavenging activity after 30 mins by UV-spectrophotometry
|
None
|
8.42
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Unusual C,O-Fused Glycosylapigenins from Serjania marginata Leaves.
Year : 2015
Volume : 78
Issue : 1
First Page : 77
Last Page : 84
Authors : Heredia-Vieira SC, Simonet AM, Vilegas W, Macías FA.
Abstract : A phytochemical study of a Serjania marginata leaf extract with antiulcer activity afforded 15 compounds, including the new 3-O-α-l-arabinopyranosyl(1→3)-α-l-rhamnopyranosyl(1→2)[β-d-glucopyranosyl(1→4)]-α-l-arabinopyranosyloleanolic acid (1) and 7,5″-anhydroapigenin 8-C-α-(2,6-dideoxy-5-hydroxy-ribo-hexopyranosyl)-4'-O-β-d-glucopyranoside (4). The structures of the new compounds were determined by spectroscopic analysis, including 1D and 2D NMR techniques, mass spectrometry, and chemical methods. Compound 4 is a C-hexopyranosylapigenin with an unusual cyclic ether linkage between C-5″ and C-7 of apigenin. The isolated proanthocyanidins have high antioxidant activities, and these compounds are probably responsible for the gastroprotective effect of the extract.
|
Inhibition of insulin fibril formation (unknown origin) assessed as turbidity at 1:5 insulin to compound ratio at pH2 up to 12 hrs by UV/vis spectrometry
|
Homo sapiens
|
50.0
%
|
|
Journal : Eur. J. Med. Chem.
Title : Gallic acid, one of the components in many plant tissues, is a potential inhibitor for insulin amyloid fibril formation.
Year : 2014
Volume : 85
First Page : 352
Last Page : 358
Authors : Jayamani J, Shanmugam G.
Abstract : Proteins under stressful conditions can lead to the formation of an ordered self-assembled structure, referred to as amyloid fibrils, to which many neurodegenerative diseases such as Type II diabetes, Alzheimer's, Parkinson's, Huntington's, etc., are attributed. Inhibition of amyloid fibril formation using natural products is one of the main therapeutic strategies to prevent the progression of these diseases. Polyphenols are the mostly consumed as antioxidants in a human nutrition. Herein, we have studied the effect of a simple polyphenol, gallic acid (GA), one of the main components in plant tissues, especially in tea leaves, on the insulin amyloid fibril formation. Different biophysical characterizations such as turbidity, atomic force microscopy (AFM), Thioflavin T (ThT) assays, circular dichroism, and Fourier transform-infrared spectroscopy have been used to analyze the inhibition of amyloid fibril formation. The occurrence of fibrils in an AFM image and ThT fluorescence enhancement confirms the formation of insulin amyloid fibrils when incubated under acidic pH 2 at 65 °C. In the presence of GA, absence of fibrils in AFM image and no change in the intensity of ThT fluorescence confirms the inhibition of insulin amyloid fibrils by GA. Spectroscopic results reveal that GA inhibits the conformational transition of α-helix → β-sheet, which is generally induced during the insulin fibril formation. It was found that the inhibitory effect of GA is concentration dependent and non-linear. Based on the observed results, we propose that GA interacts with native insulin, preventing nuclei formation, which is essential for fibril growth, thereby inhibiting the amyloid fibril formation. The present results thus demonstrate that GA can effectively inhibit insulin amyloid fibril formation in vitro.
|
Inhibition of insulin fibril formation (unknown origin) assessed as turbidity at 1:50 insulin to compound ratio at pH2 up to 12 hrs by UV/vis spectrometry
|
Homo sapiens
|
90.0
%
|
|
Journal : Eur. J. Med. Chem.
Title : Gallic acid, one of the components in many plant tissues, is a potential inhibitor for insulin amyloid fibril formation.
Year : 2014
Volume : 85
First Page : 352
Last Page : 358
Authors : Jayamani J, Shanmugam G.
Abstract : Proteins under stressful conditions can lead to the formation of an ordered self-assembled structure, referred to as amyloid fibrils, to which many neurodegenerative diseases such as Type II diabetes, Alzheimer's, Parkinson's, Huntington's, etc., are attributed. Inhibition of amyloid fibril formation using natural products is one of the main therapeutic strategies to prevent the progression of these diseases. Polyphenols are the mostly consumed as antioxidants in a human nutrition. Herein, we have studied the effect of a simple polyphenol, gallic acid (GA), one of the main components in plant tissues, especially in tea leaves, on the insulin amyloid fibril formation. Different biophysical characterizations such as turbidity, atomic force microscopy (AFM), Thioflavin T (ThT) assays, circular dichroism, and Fourier transform-infrared spectroscopy have been used to analyze the inhibition of amyloid fibril formation. The occurrence of fibrils in an AFM image and ThT fluorescence enhancement confirms the formation of insulin amyloid fibrils when incubated under acidic pH 2 at 65 °C. In the presence of GA, absence of fibrils in AFM image and no change in the intensity of ThT fluorescence confirms the inhibition of insulin amyloid fibrils by GA. Spectroscopic results reveal that GA inhibits the conformational transition of α-helix → β-sheet, which is generally induced during the insulin fibril formation. It was found that the inhibitory effect of GA is concentration dependent and non-linear. Based on the observed results, we propose that GA interacts with native insulin, preventing nuclei formation, which is essential for fibril growth, thereby inhibiting the amyloid fibril formation. The present results thus demonstrate that GA can effectively inhibit insulin amyloid fibril formation in vitro.
|
Antioxidant activity assessed as DPPH free radical scavenging activity measured as decoloration of a MeOH solution after 10 mins by spectrophotometry
|
None
|
2.79
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Iridoid glycosides from Barleria lupulina.
Year : 2015
Volume : 78
Issue : 2
First Page : 320
Last Page : 324
Authors : Kim KH, Park YJ, Chung KH, Yip ML, Clardy J, Senger D, Cao S.
Abstract : Phytochemical investigation of an extract of the aerial part of Barleria lupulina resulted in the identification of four new iridoid glycosides (1-4), together with 14 known analogues (5-18). The structures of 1-4 were determined through 1D and 2D NMR spectroscopic data analysis, HRMS, and acid hydrolysis. This is the first report of iridoid glycosides with a formate group. The free-radical scavenging activity of compounds 9, 12, and 15-17 was assessed using the DPPH assay. Compounds 16 and 17 scavenged DPPH radicals weakly with IC50 values of 97.5 and 78.6 μg/mL, respectively.
|
Inhibition of FucT-7 (unknown origin)
|
Homo sapiens
|
60.0
nM
|
|
Journal : MedChemComm
Title : Beyond substrate analogues: new inhibitor chemotypes for glycosyltransferases
Year : 2014
Volume : 5
Issue : 8
First Page : 1106
Last Page : 1125
Authors : Tedaldi L, Wagner GK
|
Antioxidant activity assessed as inhibition of allopurinol-xanthine oxidase system-mediated superoxide formation measured over 7 mins by lucigenin-based chemiluminescence analysis
|
None
|
700.0
nM
|
|
Journal : Eur. J. Med. Chem.
Title : On the vasoprotective mechanisms underlying novel β-phosphorylated nitrones: Focus on free radical characterization, scavenging and NO-donation in a biological model of oxidative stress.
Year : 2016
Volume : 119
First Page : 197
Last Page : 217
Authors : Cassien M, Petrocchi C, Thétiot-Laurent S, Robin M, Ricquebourg E, Kandouli C, Asteian A, Rockenbauer A, Mercier A, Culcasi M, Pietri S.
Abstract : A series of new hybrid 2-(diethoxyphosphoryl)-N-(benzylidene)propan-2-amine oxide derivatives with different aromatic substitution (PPNs) were synthesized. These molecules were evaluated for their EPR spin trapping potential on eleven different radicals and NO-donation properties in vitro, cytotoxicity and vasoprotective effect on precontracted rat aortic rings. A subfamily of the new PPNs featured an antioxidant moiety occurring in natural phenolic acids. From the experimental screening of these hydroxyphenyl- and methoxyphenyl-substituted PPNs, biocompatible nitrones 4d, and 4g-4i deriving from caffeic, gallic, ferulic and sinapic acids, which combined improved EPR probing of ROS formation, vasorelaxant action and antioxidant potency, might be potential drug candidate alternatives to PBN and its analogues.
|
Antioxidant activity assessed as ABTS radical scavenging activity measured after 10 mins by ABTS assay
|
None
|
350.0
nM
|
|
Journal : Eur J Med Chem
Title : Synthesis and antioxidant evaluation of desmethylxanthohumol analogs and their dimers.
Year : 2017
Volume : 125
First Page : 335
Last Page : 345
Authors : Teng Y, Li X, Yang K, Li X, Zhang Z, Wang L, Deng Z, Song B, Yan Z, Zhang Y, Lu K, Yu P.
Abstract : Four ring-closed analogs of natural prenylated chalcone desmethylxanthohumol (1) and their dimers were synthesized from the commercially available 1-(2,4,6-trihydroxyphenyl)ethan-1-one in five and six linear steps, respectively. The structures of the eight new derivatives were confirmed using1H NMR, 13C NMR and HRMS. The antioxidant activity of the new chalcone derivatives were evaluated in a PC12 cell model of H2O2-induced oxidative damage. The SAR studies suggested that the catechol motif was essential for the antioxidant activity. Moreover, the dimers showed better antioxidant activity than their corresponding monomers did. Among them, compound 14d was the most potent and increased PC12 cell viability from 25% to 85%. Flow cytometric analysis showed that compound 14d, the most potent compound, decreased the apoptotic PC12 cell percentage and significantly reduced the LDH release and 8-OHdG generation but increased the GSH levels in H2O2-treated PC12 cells. Furthermore, compound 14d had a higher FRAP value than that of gallic acid. It also reduced the stable ABTS+ free radical with a lower EC50 than that of gallic acid.
|
Inhibition of SPI-1 T3SS in Salmonella typhimurium expressing SopE2-CPG2-HA fusion protein assessed as reduction in type 3 protein secretion using Glu-CyFur as substrate at 25 uM after 4 hrs by fluorescence assay
|
Salmonella enterica subsp. enterica serovar Typhimurium
|
25.0
%
|
|
Journal : Bioorg Med Chem
Title : Epigallocatechin-3-gallate inhibits bacterial virulence and invasion of host cells.
Year : 2017
Volume : 25
Issue : 11
First Page : 2883
Last Page : 2887
Authors : Tsou LK, Yount JS, Hang HC.
Abstract : Increasing antibiotic resistance and beneficial effects of host microbiota has motivated the search for anti-infective agents that attenuate bacterial virulence rather than growth. For example, we discovered that specific flavonoids such as baicalein and quercetin from traditional medicinal plant extracts could attenuate Salmonella enterica serovar Typhimurium type III protein secretion and invasion of host cells. Here, we show epigallocatechin-3-gallate from green tea extracts also inhibits the activity of S. Typhimurium type III protein effectors and significantly reduces bacterial invasion into host cells. These results reveal additional dietary plant metabolites that can attenuate bacterial virulence and infection of host cells.
|
Antioxidant activity assessed as DPPH free radical scavenging activity
|
None
|
23.7
nM
|
|
Journal : Eur J Med Chem
Title : Free radicals and polyphenols: The redox chemistry of neurodegenerative diseases.
Year : 2017
Volume : 133
First Page : 379
Last Page : 402
Authors : Losada-Barreiro S, Bravo-Díaz C.
Abstract : The oxidation of bioorganic materials by air and, particularly, the oxidative stress involved in the cell loss and other pathologies associated with neurodegenerative diseases (NDs) are of enormous social and economic importance. NDs generally involve free radical reactions, beginning with the formation of an initiating radical by some redox, thermal or photochemical process, causing nucleic acid, protein and lipid oxidations and the production of harmful oxidative products. Physically, persons afflicted by NDs suffer progressive loss of memory and thinking ability, mood swings, personality changes, and loss of independence. Therefore, the development of antioxidant strategies to retard or minimize the oxidative degradation of bioorganic materials has been, and still is, of paramount importance. While we are aware of the importance of investigating the biological and medical aspects of the diseases, elucidation of the associated chemistry is crucial to understanding their progression, heading to intelligent chemical intervention to find more efficient therapies to prevent or delay the onset of the diseases. Accordingly, this review aims to provide the reader with a chemical base to understand the behavior and properties of the reactive oxygen species involved and of typical radical scavengers such as polyphenolic antioxidants. Some discussion on the structures of the various species, their formation, chemical reactivities and lifetimes is included. The ultimate goal is to understand how, when and where they form, how far they travel prior to react, which molecules are their targets, and how we can, eventually, control their activity to minimize their impact by means of chemical methods. Recent strategies explore chemical modifications of the hydrophobicity of potent, natural antioxidants to improve their efficiency by fine-tuning their concentrations at the reaction site.
|
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
|
-6.43
%
|
|
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.
|
Binding affinity of human recombinant FLAG-tagged ppGalNAcT2 expressed in HEK293 cells assessed as dissociation constant by SPR analysis
|
Homo sapiens
|
924.0
nM
|
|
Journal : Bioorg Med Chem
Title : Inhibition of polypeptide N-acetyl-α-galactosaminyltransferases is an underlying mechanism of dietary polyphenols preventing colorectal tumorigenesis.
Year : 2019
Volume : 27
Issue : 15
First Page : 3372
Last Page : 3382
Authors : Liu F, Cui Y, Yang F, Xu Z, Da LT, Zhang Y.
Abstract : Ellagitannin-derived ellagic acid (EA) and colonic metabolite urolithins are functional dietary ingredients for cancer prevention, but the underlying mechanism need elucidation. Mucin-type O-glycosylation, initiated by polypeptide N-acetyl-α-galactosaminyltransferases (ppGalNAc-Ts), fine-tunes multiple biological processes and is closely associated with cancer progression. Herein, we aim to explore how specific tannin-based polyphenols affect tumor behavior of colorectal cancer cells (CRC) by modulating O-glycosylation. Utilizing HPLC-based enzyme assay, we find urolithin D (UroD), EA and gallic acid (GA) potently inhibit ppGalNAc-Ts. In particular, UroD inhibits ppGalNAc-T2 through a peptide/protein-competitive manner with nanomolar affinity. Computational simulations combined with site-directed mutagenesis further support the inhibitors' mode of action. Moreover, lectin analysis and metabolic labelling reveal that UroD can reduce cell O-glycans but not N-glycans. Transwell experiments prove that UroD inhibits migration and invasion of CRC cells. Our work proves that specific tannin-based polyphenols can potently inhibit ppGalNAc-Ts activity to reduce cell O-glycosylation and lead to lowering the migration and invasion of CRC cells, suggesting that disturbance of mucin-type O-glycosylation is an important mechanism for the function of dietary polyphenols.
|
Binding affinity of human recombinant FLAG-tagged ppGalNAcT2 expressed in HEK293 cells assessed as dissociation rate by SPR analysis
|
Homo sapiens
|
1.34
10'-3/s
|
|
Journal : Bioorg Med Chem
Title : Inhibition of polypeptide N-acetyl-α-galactosaminyltransferases is an underlying mechanism of dietary polyphenols preventing colorectal tumorigenesis.
Year : 2019
Volume : 27
Issue : 15
First Page : 3372
Last Page : 3382
Authors : Liu F, Cui Y, Yang F, Xu Z, Da LT, Zhang Y.
Abstract : Ellagitannin-derived ellagic acid (EA) and colonic metabolite urolithins are functional dietary ingredients for cancer prevention, but the underlying mechanism need elucidation. Mucin-type O-glycosylation, initiated by polypeptide N-acetyl-α-galactosaminyltransferases (ppGalNAc-Ts), fine-tunes multiple biological processes and is closely associated with cancer progression. Herein, we aim to explore how specific tannin-based polyphenols affect tumor behavior of colorectal cancer cells (CRC) by modulating O-glycosylation. Utilizing HPLC-based enzyme assay, we find urolithin D (UroD), EA and gallic acid (GA) potently inhibit ppGalNAc-Ts. In particular, UroD inhibits ppGalNAc-T2 through a peptide/protein-competitive manner with nanomolar affinity. Computational simulations combined with site-directed mutagenesis further support the inhibitors' mode of action. Moreover, lectin analysis and metabolic labelling reveal that UroD can reduce cell O-glycans but not N-glycans. Transwell experiments prove that UroD inhibits migration and invasion of CRC cells. Our work proves that specific tannin-based polyphenols can potently inhibit ppGalNAc-Ts activity to reduce cell O-glycosylation and lead to lowering the migration and invasion of CRC cells, suggesting that disturbance of mucin-type O-glycosylation is an important mechanism for the function of dietary polyphenols.
|
Inhibition of human TAS2R39 expressed in HEK293 cells coexpressing G-protein at 10 mM assessed as reduction in epicatechin gallate-induced intracellular calcium release by Fluo-4-AM dye based fluorescence assay relative to control
|
Homo sapiens
|
25.0
%
|
|
Title : Flavan-3-ol containing foodstuffs
|
Antioxidant activity assessed as DPPH radical scavenging activity after 5 mins by spectrophotometric analysis
|
None
|
7.2
ug.mL-1
|
|
Journal : J Nat Prod
Title : Minor Pyranonaphthoquinones from the Apothecia of the Lichen Ophioparma ventosa.
Year : 2016
Volume : 79
Issue : 4
First Page : 1005
Last Page : 1011
Authors : Le Pogam P, Le Lamer AC, Siva B, Legouin B, Bondon A, Graton J, Jacquemin D, Rouaud I, Ferron S, Obermayer W, Babu KS, Boustie J.
Abstract : Four new quinonoid naphthopyranones, ophioparmin (1), 4-methoxyhaemoventosins (2a and 2b), and 4-hydroxyhaemoventosin (3), together with anhydrofusarubin lactone (4) and haemoventosin (5) were isolated from the fruiting bodies of Ophioparma ventosa, a crustose lichen. Their structures were determined by spectroscopic analyses, and the absolute configurations of 1 and 2 were elucidated through experimental and calculated electronic circular dichroism analyses. Compounds 1, 2, and 5 exhibited moderate to strong antioxidant activities. The main pigment haemoventosin exhibited significant cytotoxicity toward a panel of nine cell lines.
|
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate
|
Severe acute respiratory syndrome coronavirus 2
|
64.71
%
|
|
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate
|
Severe acute respiratory syndrome coronavirus 2
|
59.39
%
|
|
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
|
1.29
%
|
|
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
|
-0.01
%
|
|
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
|
1.29
%
|
|
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
|
-0.01
%
|
|
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.
|
Inhibition of alpha-synuclein aggregation (unknown origin) at 30 uM incubated for 3 days by thioflavin T based fluorescence assay relative to control
|
Homo sapiens
|
78.2
%
|
|
Journal : Bioorg Med Chem
Title : Amide derivatives of Gallic acid: Design, synthesis and evaluation of inhibitory activities against in vitro α-synuclein aggregation.
Year : 2020
Volume : 28
Issue : 15
First Page : 115596
Last Page : 115596
Authors : Chen L, Huang GL, Lü MH, Zhang YX, Xu J, Bai SP.
Abstract : Gallic acid (GA), a natural phenolic acid, has received numerous attention because of its anti-oxidative, anti-inflammatory, and anti-cancer activity. More importantly, GA can act as an efficient inhibitor of α-Synuclein (α-Syn) aggregation at early stages. Nevertheless, some evidences suggest that GA is unlikely to cross the blood-brain barrier because of its high hydrophilicity. Hence, GA may not be considered as a promising candidate or entering brain and directly affecting the central nervous system. Accordingly, we have designed and synthesized a series of amide derivatives of GA, some of which possess appropriate lipophilicity and hydrophilicity with LogP (2.09-2.79). Meanwhile, these sheet-like conjugated compounds have good π-electron delocalization and high ability of hydrogen-bond formation. Some compounds have shown better in vitro anti-aggregation activities than GA towards α-Syn, with IC<sub>50</sub> down to 0.98 μM. The valid modification strategy of GA is considered an efficient way to discover novel inhibitors of α-Syn aggregation.
