|
Compound was evaluated for inhibition constant, in liver microsomes from 3-methylcholanthrene-exposed rats
|
Rattus norvegicus
|
33.0
nM
|
|
Journal : J. Med. Chem.
Title : Effects of 1-arylpyrroles and naphthoflavones upon cytochrome P-450 dependent monooxygenase activities.
Year : 1981
Volume : 24
Issue : 7
First Page : 822
Last Page : 830
Authors : Viswanathan T, Alworth WL.
Abstract : The inhibitions of cytochrome P-450 dependent monooxygenase activity in microsomes from rat liver by 1-phenylpyrrole, 1-(2-isopropylphenyl)pyrrole, 4(5)-phenylimidazole, and 1-(2-isopropylphenyl)imidazole have been compared. The results establish that the presence of an imidazole N-3 nitrogen substituent is not required to inhibit the monooxygenase activity measured by the deethylation of 7-ethoxycoumarin. The presence of an appropriately situated N-3 atom, however, as in 1-(2-isopropylphenyl)imidazole, significantly decreases both the Ki and alphaKi of these mixed type inhibitors. The induction of 7-ethoxycoumarin deethylase activity in the microsomal fraction from rat liver by alpha-naphthoflavone, beta-naphthoflavone, and 3-methylcholanthrene and the inhibition of these activities by flavone and alpha-, beta, and gamma-naphthoflavone have also been examined. The results establish that alpha-naphthoflavone is the most effective in vitro inhibitor. The results also indicate that the microsomal monooxygenase activities induced in rat liver by alpha-naphthoflavone, beta-naphthoflavone, and 3-methylcholanthrene are not equivalent. Based upon the observed results, it is concluded that differential effects of alpha- and beta-naphthoflavone on aryl hydrocarbon skin tumorigenesis may be the result of differential enzyme induction rather than the result of differential enzyme inhibition.
|
Compound was evaluated for inhibition constant, in liver microsomes from beta-naphthoflavone-exposed rats
|
Rattus norvegicus
|
190.0
nM
|
|
Journal : J. Med. Chem.
Title : Effects of 1-arylpyrroles and naphthoflavones upon cytochrome P-450 dependent monooxygenase activities.
Year : 1981
Volume : 24
Issue : 7
First Page : 822
Last Page : 830
Authors : Viswanathan T, Alworth WL.
Abstract : The inhibitions of cytochrome P-450 dependent monooxygenase activity in microsomes from rat liver by 1-phenylpyrrole, 1-(2-isopropylphenyl)pyrrole, 4(5)-phenylimidazole, and 1-(2-isopropylphenyl)imidazole have been compared. The results establish that the presence of an imidazole N-3 nitrogen substituent is not required to inhibit the monooxygenase activity measured by the deethylation of 7-ethoxycoumarin. The presence of an appropriately situated N-3 atom, however, as in 1-(2-isopropylphenyl)imidazole, significantly decreases both the Ki and alphaKi of these mixed type inhibitors. The induction of 7-ethoxycoumarin deethylase activity in the microsomal fraction from rat liver by alpha-naphthoflavone, beta-naphthoflavone, and 3-methylcholanthrene and the inhibition of these activities by flavone and alpha-, beta, and gamma-naphthoflavone have also been examined. The results establish that alpha-naphthoflavone is the most effective in vitro inhibitor. The results also indicate that the microsomal monooxygenase activities induced in rat liver by alpha-naphthoflavone, beta-naphthoflavone, and 3-methylcholanthrene are not equivalent. Based upon the observed results, it is concluded that differential effects of alpha- and beta-naphthoflavone on aryl hydrocarbon skin tumorigenesis may be the result of differential enzyme induction rather than the result of differential enzyme inhibition.
|
In vitro inhibition of aminopeptidase N (APN) activity in intact U937 cells in presence of Ala-pNA and 10e-3 M concentration of compound
|
None
|
5.0
%
|
|
Journal : J. Med. Chem.
Title : Synthesis and biological evaluation of novel flavone-8-acetic acid derivatives as reversible inhibitors of aminopeptidase N/CD13.
Year : 2003
Volume : 46
Issue : 18
First Page : 3900
Last Page : 3913
Authors : Bauvois B, Puiffe ML, Bongui JB, Paillat S, Monneret C, Dauzonne D.
Abstract : The cell surface aminopeptidase N (APN/CD13), overexpressed in tumor cells, plays a critical role in angiogenesis. However, potent, selective, and, particularly, noncytotoxic inhibitors ot this protein are lacking, and the present work was undertaken with the aim of developing a new generation of noncytotoxic inhibitors that bind to APN/CD13. In this context, we have synthesized a series of novel flavone-8-acetic acid derivatives. Among the herein described and evaluated compounds, the 2',3-dinitroflavone-8-acetic acid (19b) proved to be the most efficient and exhibited an IC(50) of 25 microM which is 2.5 times higher than that of bestatin (1), the natural known inhibitor of APN/CD13. However, in contrast to bestatin (1), the dinitroflavone 19b did not induce any cytotoxicity to cultured human model cells. The presence of other substituents such as NO(2) or OCH(3) groups at the 3'- or 4'-position of the B phenyl group, or the existence of steric constraints (compounds 24 and 29), did not improve selectivity and potency. The flavone 19b affinity for APN/CD13 is not recovered with other proteases such as matrix metalloproteinase-9 (MMP-9), angiotensin converting enzyme (ACE/CD143), neutral endopeptidase (NEP/CD10), gamma-glutamyl transpeptidase (CD224), or the serine proteases dipeptidyl peptidase IV (DPPIV/CD26) or cathepsin G.
|
Inhibition of binding to GABA-A Benzodiazepine receptor
|
None
|
17.0
nM
|
|
Journal : J. Med. Chem.
Title : Mixture-based synthetic combinatorial libraries.
Year : 1999
Volume : 42
Issue : 19
First Page : 3743
Last Page : 3778
Authors : Houghten RA, Pinilla C, Appel JR, Blondelle SE, Dooley CT, Eichler J, Nefzi A, Ostresh JM.
|
Evaluated for inhibition of COX-2 catalyzed PGE-2 production from LPS induced RAW 264.7 cells
|
Mus musculus
|
500.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis and inhibitory activity against COX-2 catalyzed prostaglandin production of chrysin derivatives.
Year : 2004
Volume : 14
Issue : 5
First Page : 1165
Last Page : 1167
Authors : Dao TT, Chi YS, Kim J, Kim HP, Kim S, Park H.
Abstract : A series of chrysin derivatives were prepared and evaluated for their inhibitory activities of cyclooxygenase-2 catalyzed prostaglandin production. Chrysin derivatives were prepared from 2-hydroxyacetophenone, 2,4-dihydroxyacetophenone and 2,6-dihydroxyacetophenone in 2 to 4 steps, respectively. Methxoylated chrysin derivatives were converted to the corresponding hydroxylated chrysin derivatives by the reaction with BBr(3) in good yields. The inhibitory activity of the chrysin derivatives against prostaglandin production from lipopolysaccharide-treated RAW 264.7 cells was measured. We found that chrysin derivatives with 3',4'-dichloro substituents (5e, 6e and 7e) exhibited good inhibitory activity of prostaglandin production.
|
Inhibition of COX-2 catalyzed PGE-2 production from LPS induced RAW 264.7 cells at concentration of 10 uM
|
None
|
92.2
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Synthesis and inhibitory activity against COX-2 catalyzed prostaglandin production of chrysin derivatives.
Year : 2004
Volume : 14
Issue : 5
First Page : 1165
Last Page : 1167
Authors : Dao TT, Chi YS, Kim J, Kim HP, Kim S, Park H.
Abstract : A series of chrysin derivatives were prepared and evaluated for their inhibitory activities of cyclooxygenase-2 catalyzed prostaglandin production. Chrysin derivatives were prepared from 2-hydroxyacetophenone, 2,4-dihydroxyacetophenone and 2,6-dihydroxyacetophenone in 2 to 4 steps, respectively. Methxoylated chrysin derivatives were converted to the corresponding hydroxylated chrysin derivatives by the reaction with BBr(3) in good yields. The inhibitory activity of the chrysin derivatives against prostaglandin production from lipopolysaccharide-treated RAW 264.7 cells was measured. We found that chrysin derivatives with 3',4'-dichloro substituents (5e, 6e and 7e) exhibited good inhibitory activity of prostaglandin production.
|
Inhibition of beef heart mitochondrial NADH oxidase assessed per mg of protein
|
Bos taurus
|
240.0
nM
|
|
Journal : J. Nat. Prod.
Title : Inhibition of mitochondrial NADH oxidase, succinoxidase, and ATPase by naturally occurring flavonoids.
Year : 1987
Volume : 50
Issue : 3
First Page : 427
Last Page : 433
Authors : Bohmont C, Aaronson LM, Mann K, Pardini RS.
Abstract : A structure-activity investigation of the inhibition of beef heart mitochondrial NADH oxidase and succinoxidase and rat liver mitochondrial ATPase by flavonoids was conducted. NADH oxidase was the most sensitive to inhibition by flavonoids: 13 of the 18 flavonoids tested inhibited NADH oxidase, whereas only 4 and 5 flavonoids inhibited succinoxidase and ATPase, respectively. The flavonoids possessing a catechol or pyrogallol moiety, and a 2,3-double bond and a 3-hydroxyl group were the most inhibitory towards the respiratory chain enzymes. The catechol or pyrogallol moiety did not exert preferential activity towards the oligomycin-sensitive ATPase because morin, which contains a meta-dihydroxy configuration, was the most potent ATPase inhibitor.
|
Inhibition of cow milk xanthine oxidase at 50 ug/mL
|
Bos taurus
|
15.4
%
|
|
Journal : J. Nat. Prod.
Title : Inhibition of cow's milk xanthine oxidase by flavonoids.
Year : 1988
Volume : 51
Issue : 2
First Page : 345
Last Page : 348
Authors : Hayashi T, Sawa K, Kawasaki M, Arisawa M, Shimizu M, Morita N.
|
Pesticidal activity against Dermatophagoides pteronyssinus after 24 hrs
|
Dermatophagoides pteronyssinus
|
0.5
g/m2
|
|
Journal : J. Nat. Prod.
Title : Acaricidal activity of tonka bean extracts. Synthesis and structure-activity relationships of bioactive derivatives.
Year : 2003
Volume : 66
Issue : 5
First Page : 690
Last Page : 692
Authors : Gleye C, Lewin G, Laurens A, Jullian JC, Loiseau P, Bories C, Hocquemiller R.
Abstract : The acaricidal effects of tonka bean, Dipterix odorata, extracts were investigated on Dermatophagoides pteronyssinus, the European house dust mite, and compared with benzyl benzoate as a standard acaricidal compound. A cyclohexane extract was the most effective, with an EC(50) = 0.075 g/m(2) after a 24 h period, as compared with benzyl benzoate (0.025 g/m(2)). Bioassay-guided fractionation of this extract led to the isolation of coumarin (1). Pharmacomodulation of this compound led us to test 20 analogues (2-21), which were either synthesized or purchased.
|
Inhibition of EGFR in human A431 cells
|
Homo sapiens
|
50.0
ug.mL-1
|
|
Journal : J. Nat. Prod.
Title : Protein-tyrosine kinase inhibition: mechanism-based discovery of antitumor agents.
Year : 1992
Volume : 55
Issue : 11
First Page : 1529
Last Page : 1560
Authors : Chang CJ, Geahlen RL.
Abstract : Protein-tyrosine kinases (PTKs) have been shown to induce the cascade of altered cell parameters characteristic of transformed cells. This proposition provides an important rationale for the discovery of potential antitumor agents from natural sources on the basis of inhibition of PTK activity. Numerous naturally occurring and synthetic analogues of PTK inhibitors were systematically evaluated in this review based on their structure-activity relationships and potential antitumor efficacy.
|
Antimalarial activity against Plasmodium falciparum DD2 by [3H]hypoxanthine uptake
|
Plasmodium falciparum
|
2.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Type II NADH dehydrogenase of the respiratory chain of Plasmodium falciparum and its inhibitors.
Year : 2009
Volume : 19
Issue : 3
First Page : 972
Last Page : 975
Authors : Dong CK, Patel V, Yang JC, Dvorin JD, Duraisingh MT, Clardy J, Wirth DF.
Abstract : Plasmodium falciparum NDH2 (pfNDH2) is a non-proton pumping, rotenone-insensitive alternative enzyme to the multi-subunit NADH:ubiquinone oxidoreductases (Complex I) of many other eukaryotes. Recombinantly expressed pfNDH2 prefers coenzyme CoQ(0) as an acceptor substrate, and can also use the artificial electron acceptors, menadione and dichlorophenol-indophenol (DCIP). Previously characterized NDH2 inhibitors, dibenziodolium chloride (DPI), diphenyliodonium chloride (IDP), and 1-hydroxy-2-dodecyl-4(1H)quinolone (HDQ) do not inhibit pfNDH2 activity. Here, we provide evidence that HDQ likely targets another P. falciparum mitochondrial enzyme, dihydroorotate dehydrogenase (pfDHOD), which is essential for de novo pyrimidine biosynthesis.
|
Inhibition of PDE4 in human U937 cells assessed as inhibition of cAMP hydrolysis at 11 uM by SPA
|
Homo sapiens
|
50.0
%
|
|
Journal : J. Nat. Prod.
Title : Polymethoxylated flavones derived from citrus suppress tumor necrosis factor-alpha expression by human monocytes.
Year : 1999
Volume : 62
Issue : 3
First Page : 441
Last Page : 444
Authors : Manthey JA, Grohmann K, Montanari A, Ash K, Manthey CL.
Abstract : Flavonoids isolated from citrus were evaluated for their ability to affect the inflammation response through suppression of cytokine expression by human monocytes. Several polymethoxylated flavones inhibited lipopolysaccharide-induced monocyte expression of tumor necrosis factor (TNFalpha). Subsequent studies centered on the compound 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF) which produced the highest inhibition (IC50 = 5 microM). HMF was also a potent inhibitor of macrophage inflammatory protein-1alpha (MIP-1alpha) and interleukin-10 (IL-10) production, but not of IL-1beta, IL-6, or IL-8 production. Suppression of TNFalpha production was at the level of mRNA induction as determined by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). HMF was also a potent inhibitor of human phosphodiesterase activity and was shown to induce a substantial elevation of cAMP levels in monocytes. The similarity of these results to the inhibition profile of the known phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, suggests that the polymethoxylated flavones inhibit cytokine production in part by suppression of phosphodiesterase activity. The ability of HMF to also inhibit IL-10 production suggests the additional existence of a phosphodiesterase-independent mechanism for this compound.
|
Inhibition of human recombinant MAOA expressed in BTI-TN-5B1-4 cells at 100 uM by para-tyramine oxidation assay
|
Homo sapiens
|
40.0
%
|
|
Journal : Bioorg. Med. Chem.
Title : A new series of flavones, thioflavones, and flavanones as selective monoamine oxidase-B inhibitors.
Year : 2010
Volume : 18
Issue : 3
First Page : 1273
Last Page : 1279
Authors : Chimenti F, Fioravanti R, Bolasco A, Chimenti P, Secci D, Rossi F, Yáñez M, Orallo F, Ortuso F, Alcaro S, Cirilli R, Ferretti R, Sanna ML.
Abstract : A new series of synthetic flavones, thioflavones, and flavanones has been synthesized and evaluated as potential inhibitors of monoamine oxidase isoforms (MAO-A and -B). The most active series is the flavanone one with higher selective inhibitory activity against MAO-B. Some of these flavanones (mainly the most effective) have been separated and tested as single enantiomers. In order to investigate the MAOs recognition of the most active and selective compounds, a molecular modeling study has been performed using available Protein Data Bank (PDB) structures as receptor models for docking experiments.
|
Inhibition of human placental microsome CYP19
|
Homo sapiens
|
8.0
nM
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Pharmacophore modeling strategies for the development of novel nonsteroidal inhibitors of human aromatase (CYP19).
Year : 2010
Volume : 20
Issue : 10
First Page : 3050
Last Page : 3064
Authors : Muftuoglu Y, Mustata G.
Abstract : The present study utilizes for the first time the structural information of aromatase, an important pharmacological target in anti-breast cancer therapy, to extract the pharmacophoric features important for interactions between the enzyme and its substrate, androstenedione. A ligand-based pharmacophore model developed from the most comprehensive list of nonsteroidal aromatase inhibitors (AIs) is described and explained, as well. This study demonstrates that the ligand-based pharmacophore model contributes to efficacy while the structure-based model contributes to specificity. It is also shown that a 'merged' model (i.e., a merged structure-based and ligand-based model) can successfully identify known AIs and differentiate between active and inactive inhibitors. Therefore, this model can be effectively used to identify the next generation of highly specific and less toxic aromatase inhibitors for breast cancer treatment.
|
Inhibition of human 11beta HSD1 in HEK293 cells at 10 uM
|
Homo sapiens
|
16.0
%
|
|
Journal : Eur. J. Med. Chem.
Title : A comparative study of flavonoid analogues on streptozotocin-nicotinamide induced diabetic rats: quercetin as a potential antidiabetic agent acting via 11beta-hydroxysteroid dehydrogenase type 1 inhibition.
Year : 2010
Volume : 45
Issue : 6
First Page : 2606
Last Page : 2612
Authors : Torres-Piedra M, Ortiz-Andrade R, Villalobos-Molina R, Singh N, Medina-Franco JL, Webster SP, Binnie M, Navarrete-Vázquez G, Estrada-Soto S, Estrada-Soto S.
Abstract : The aim of the current study was to investigate the oral antidiabetic activity of six structurally related flavonoids: flavone (1), 3-hydroxyflavone (2), 6-hydroxyflavone (3), 7-hydroxyflavone (4), chrysin (5) and quercetin (6). Normoglycemic and STZ-nicotinamide diabetic rats were treated with these flavonoids (50 mg/kg) and the hypoglycemic and antidiabetic effects in acute and sub acute (five days of treatment) experiments were determined. Compounds 1, 5 and 6 were found most active in both experiments in comparison with control group (p<0.05). After five days of administration to STZ-nicotinamide diabetic rats, flavonoids induced a significantly diminishing of total cholesterol, TG and LDL and an augment of HDL compared with the control group (p<0.05). The in vitro inhibitory activity of the compounds against 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) was also evaluated. Quercetin, the most active compound, was docked into the crystal structure of 11beta-HSD1. Docking results indicate potential hydrogen bond interactions with hydroxyl groups of catalytic amino acid residues.
|
Inhibition of Trypanosoma cruzi triosephosphate isomerase at 100 uM after 2 hrs
|
Trypanosoma cruzi
|
52.0
%
|
|
Journal : Eur. J. Med. Chem.
Title : Massive screening yields novel and selective Trypanosoma cruzi triosephosphate isomerase dimer-interface-irreversible inhibitors with anti-trypanosomal activity.
Year : 2010
Volume : 45
Issue : 12
First Page : 5767
Last Page : 5772
Authors : Alvarez G, Aguirre-López B, Varela J, Cabrera M, Merlino A, López GV, Lavaggi ML, Porcal W, Di Maio R, González M, Cerecetto H, Cabrera N, Pérez-Montfort R, de Gómez-Puyou MT, Gómez-Puyou A.
Abstract : Triosephosphate isomerase from Trypanosoma cruzi (TcTIM), an enzyme in the glycolytic pathway that exhibits high catalytic rates of glyceraldehyde-3-phosphate- and dihydroxyacetone-phosphate-isomerization only in its dimeric form, was screened against an in-house chemical library containing nearly 230 compounds belonging to different chemotypes. After secondary screening, twenty-six compounds from eight different chemotypes were identified as screening positives. Four compounds displayed selectivity for TcTIM over TIM from Homo sapiens and, concomitantly, in vitro activity against T. cruzi.
|
Inhibition of Trypanosoma cruzi triosephosphate isomerase at 400 uM after 2 hrs
|
Trypanosoma cruzi
|
83.0
%
|
|
Journal : Eur. J. Med. Chem.
Title : Massive screening yields novel and selective Trypanosoma cruzi triosephosphate isomerase dimer-interface-irreversible inhibitors with anti-trypanosomal activity.
Year : 2010
Volume : 45
Issue : 12
First Page : 5767
Last Page : 5772
Authors : Alvarez G, Aguirre-López B, Varela J, Cabrera M, Merlino A, López GV, Lavaggi ML, Porcal W, Di Maio R, González M, Cerecetto H, Cabrera N, Pérez-Montfort R, de Gómez-Puyou MT, Gómez-Puyou A.
Abstract : Triosephosphate isomerase from Trypanosoma cruzi (TcTIM), an enzyme in the glycolytic pathway that exhibits high catalytic rates of glyceraldehyde-3-phosphate- and dihydroxyacetone-phosphate-isomerization only in its dimeric form, was screened against an in-house chemical library containing nearly 230 compounds belonging to different chemotypes. After secondary screening, twenty-six compounds from eight different chemotypes were identified as screening positives. Four compounds displayed selectivity for TcTIM over TIM from Homo sapiens and, concomitantly, in vitro activity against T. cruzi.
|
Inhibition of NF-kappaB activation expressed in HCT116 cells assessed as inhibition of TNF-alpha-induced transcriptional activation at 10 uM after 12 hrs by luciferase reporter gene assay relative to control
|
None
|
113.49
%
|
|
Journal : Bioorg. Med. Chem. Lett.
Title : Relationship between the structures of flavonoids and their NF-κB-dependent transcriptional activities.
Year : 2011
Volume : 21
Issue : 20
First Page : 6036
Last Page : 6041
Authors : Shin SY, Woo Y, Hyun J, Yong Y, Koh D, Lee YH, Lim Y.
Abstract : It has been previously shown that some flavonoids inhibit NF-κB; however, the structure-activity relationships between chalcone, flavanone, flavone, and isoflavone derivatives and their TNFα induced NF-κB inhibitory effects on HCT116 human colon cancer cells have not yet been reported. Therefore, in this study, the effects of flavonoid structure on inhibition of NF-κB were investigated. Based on the combined results of this study, the structure of the flavonoids was shown to affect NF-κB activation.
|
Antioxidant activity assessed as inhibition of DPPH radical production at 33 uM after 5 min by spectrophotometric analysis
|
None
|
1.5
%
|
|
Journal : Med Chem Res
Title : Quantum chemical QSAR study of flavones and their radical-scavenging activity
Year : 2007
Volume : 16
Issue : 7
First Page : 408
Last Page : 417
Authors : Pasha FA, Cho SJ, Beg Y, Tripathi YB
|
Antioxidant activity in Wistar albino Rattus norvegicus (rat) liver microsomes assessed as inhibition of lipid peroxidation after 1 hr by TBARS method
|
Rattus norvegicus
|
100.0
ug.mL-1
|
|
Journal : Med Chem Res
Title : Synthesis of B-ring substituted flavones and evaluation of their antitumor and antioxidant activities
Year : 2013
Volume : 22
Issue : 9
First Page : 4293
Last Page : 4299
Authors : Joshi AJ, Gadhwal MK, Joshi UJ, DMello P, Sinha R, Govil G
|
Inhibition of human 6XHis-tagged TNKS2 ART domain (946 to 1161 amino acid residues) expressed in Escherichia coli Rosetta2 (DE3) by fluorescence assay
|
Homo sapiens
|
147.91
nM
|
|
Inhibition of human 6XHis-tagged TNKS2 ART domain (946 to 1161 amino acid residues) expressed in Escherichia coli Rosetta2 (DE3) by fluorescence assay
|
Homo sapiens
|
140.0
nM
|
|
Journal : J. Med. Chem.
Title : Screening and structural analysis of flavones inhibiting tankyrases.
Year : 2013
Volume : 56
Issue : 9
First Page : 3507
Last Page : 3517
Authors : Narwal M, Haikarainen T, Fallarero A, Vuorela PM, Lehtiö L.
Abstract : Flavonoids are known for their beneficial effects on human health, and therefore the therapeutic potential of these compounds have been extensively studied. Flavone has been previously identified as a tankyrase inhibitor, and to further elucidate whether tankyrases would be inhibited by other flavonoids, we performed a systematic screening of tankyrase 2 inhibitory activity using 500 natural and naturally derived flavonoids covering nine different flavonoid classes. All identified tankyrase inhibitors were flavones. We report crystal structures of all the hit compounds in complex with the catalytic domain of human tankyrase 2. Flavone derivatives in all 10 crystal structures bind to the nicotinamide binding site of tankyrase 2. Potencies of the active flavones toward tankyrases vary between 50 nM and 1.1 μM, and flavones show up to 200-fold selectivity for tankyrases over ARTD1. The molecular details of the interactions revealed by cocrystal structures efficiently describe the properties of potent flavone derivatives inhibiting tankyrases.
|
Inhibition of human 6XHis-tagged TNKS1 SAM-ART domain (1030 to 1317 amino acid residues) by fluorescence assay
|
Homo sapiens
|
323.59
nM
|
|
Inhibition of human 6XHis-tagged TNKS1 SAM-ART domain (1030 to 1317 amino acid residues) by fluorescence assay
|
Homo sapiens
|
320.0
nM
|
|
Journal : J. Med. Chem.
Title : Screening and structural analysis of flavones inhibiting tankyrases.
Year : 2013
Volume : 56
Issue : 9
First Page : 3507
Last Page : 3517
Authors : Narwal M, Haikarainen T, Fallarero A, Vuorela PM, Lehtiö L.
Abstract : Flavonoids are known for their beneficial effects on human health, and therefore the therapeutic potential of these compounds have been extensively studied. Flavone has been previously identified as a tankyrase inhibitor, and to further elucidate whether tankyrases would be inhibited by other flavonoids, we performed a systematic screening of tankyrase 2 inhibitory activity using 500 natural and naturally derived flavonoids covering nine different flavonoid classes. All identified tankyrase inhibitors were flavones. We report crystal structures of all the hit compounds in complex with the catalytic domain of human tankyrase 2. Flavone derivatives in all 10 crystal structures bind to the nicotinamide binding site of tankyrase 2. Potencies of the active flavones toward tankyrases vary between 50 nM and 1.1 μM, and flavones show up to 200-fold selectivity for tankyrases over ARTD1. The molecular details of the interactions revealed by cocrystal structures efficiently describe the properties of potent flavone derivatives inhibiting tankyrases.
|
Inhibition of oxidative burst in PMA-stimulated human neutrophils assessed as inhibition of ROS-induced luminol oxidation up to 100 uM incubated for 5 mins prior to PMA challenge by chemiluminescence assay
|
Homo sapiens
|
40.0
%
|
|
Journal : Eur. J. Med. Chem.
Title : Modulation of human neutrophils' oxidative burst by flavonoids.
Year : 2013
Volume : 67
First Page : 280
Last Page : 292
Authors : Ribeiro D, Freitas M, Tomé SM, Silva AM, Porto G, Fernandes E.
Abstract : Inflammation is a normal response towards tissue injury, but may become deleterious to the organism if uncontrolled. The overproduction of reactive species during the inflammatory process may cause or magnify the damage at inflammatory sites. Flavonoids have been suggested as therapeutic agents to avoid such damage, as these compounds exhibit anti-inflammatory activity, through the modulation of oxidative stress and signalling pathways. Both effects may attenuate neutrophils' activities at inflammatory sites. In this study, we investigated the structure/activity relationship of a series of flavonoids on the oxidative burst of human neutrophils in vitro, as a measure of its anti-inflammatory potential. Neutrophils were stimulated with phorbol-12-myristate-13-acetate, and fluorescence and chemiluminescence techniques were used to evaluate the generation of reactive oxygen species. All the tested flavonoids revealed the ability to modulate the neutrophil's oxidative burst. From the obtained results, the pivotal role of the catechol group in the B-ring was evidenced as well as the minor importance of the hydroxylations in the A-ring, which did not appear to be determinant for the activity, although clearly influencing the lipophilicity of the tested flavonoids. It is also clarified the importance of the methylation in the OH group at the B-ring catechol moiety. In conclusion, the obtained results uncover new possible strategies for the resolution of inflammatory processes, using flavonoids to modulate neutrophil's oxidative burst.
|
Inhibition of human TNKS1 (1030 to 1317) using NAD+ as substrate by fluorescence assay
|
Homo sapiens
|
323.59
nM
|
|
Inhibition of human TNKS1 (1030 to 1317) using NAD+ as substrate by fluorescence assay
|
Homo sapiens
|
330.0
nM
|
|
Journal : J. Med. Chem.
Title : Discovery of tankyrase inhibiting flavones with increased potency and isoenzyme selectivity.
Year : 2013
Volume : 56
Issue : 20
First Page : 7880
Last Page : 7889
Authors : Narwal M, Koivunen J, Haikarainen T, Obaji E, Legala OE, Venkannagari H, Joensuu P, Pihlajaniemi T, Lehtiö L.
Abstract : Tankyrases are ADP-ribosyltransferases that play key roles in various cellular pathways, including the regulation of cell proliferation, and thus, they are promising drug targets for the treatment of cancer. Flavones have been shown to inhibit tankyrases and we report here the discovery of more potent and selective flavone derivatives. Commercially available flavones with single substitutions were used for structure-activity relationship studies, and cocrystal structures of the 18 hit compounds were analyzed to explain their potency and selectivity. The most potent inhibitors were also tested in a cell-based assay, which demonstrated that they effectively antagonize Wnt signaling. To assess selectivity, they were further tested against a panel of homologous human ADP-ribosyltransferases. The most effective compound, 22 (MN-64), showed 6 nM potency against tankyrase 1, isoenzyme selectivity, and Wnt signaling inhibition. This work forms a basis for rational development of flavones as tankyrase inhibitors and guides the development of other structurally related inhibitors.
|
Inhibition of 5-LOX-mediated LTB4 production in human neutrophils using arachidonic acid as substrate at 40 uM preincubated for 10 mins followed by substrate addition measured after 8 mins by enzyme immunoassay relative to control
|
Homo sapiens
|
50.0
%
|
|
Journal : Eur. J. Med. Chem.
Title : Inhibition of LOX by flavonoids: a structure-activity relationship study.
Year : 2014
Volume : 72
First Page : 137
Last Page : 145
Authors : Ribeiro D, Freitas M, Tomé SM, Silva AM, Porto G, Cabrita EJ, Marques MM, Fernandes E.
Abstract : The lipoxygenase (LOX) products have been identified as mediators of a series of inflammatory diseases, namely rheumatoid arthritis, inflammatory bowel disease, psoriasis, allergic rhinitis, atherosclerosis and certain types of cancer. Hence, LOX inhibitors are of interest for the modulation of these phenomena and resolution of the inflammatory processes. During LOX activity, peroxyl radical complexes are part of the reaction and may function as sources of free radicals. Thus antioxidants, such as flavonoids, capable of inhibiting lipid peroxidation and scavenging free radicals, may act as LOX inhibitors. The aim of this work was to assess the structure-activity relationship among a series of flavonoids concerning 5-LOX inhibition, through a systematic study of the inhibition of the formation of LTB4 in human neutrophils. The type of inhibition of the flavonoids was further studied using soybean LOX, type I, and Saturation Transfer Difference (1)H NMR (STD-(1)H NMR) was used to characterize the binding epitopes of the compounds to LOX-1. The obtained results reinforce flavonoids as effective inhibitors of LTB4 production in human neutrophils. It was also possible to establish a structure/activity relationship for the inhibitory activity and the type of inhibition.
|
Antioxidant activity assessed as DPPH radical scavenging activity after 30 mins
|
None
|
100.0
ug.mL-1
|
|
Journal : Eur. J. Med. Chem.
Title : Localization and interaction of hydroxyflavones with lipid bilayer model membranes: a study using DSC and multinuclear NMR.
Year : 2014
Volume : 80
First Page : 285
Last Page : 294
Authors : Sinha R, Joshi A, Joshi UJ, Srivastava S, Govil G.
Abstract : The localization and interaction of six naturally occurring flavones (FLV, 5HF, 6HF, 7HF, CHY and BLN) in DPPC bilayers were studied using DSC and multi-nuclear NMR. DSC results indicate that FLV and 6HF interact with alkyl chains. The (1)H NMR shows interaction of flavones with the sn-glycero region. Ring current induced chemical shifts indicate that 6HF and BLN acquire parallel orientation in bilayers. 2D NOESY spectra indicate partitioning of the B-ring into the alkyl chain region. The DSC, NMR and binding studies indicate that 5HF and 7HF are located near head group region, while 6HF, CHY and BLN are located in the vicinity of sn-glycero region, and FLV is inserted deepest in the membrane.
|
Inhibition of PMA-induced oxidative burst in human neutrophils at 50 uM by chemiluminescence assay
|
Homo sapiens
|
40.0
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis of chlorinated flavonoids with anti-inflammatory and pro-apoptotic activities in human neutrophils.
Year : 2014
Volume : 86
First Page : 153
Last Page : 164
Authors : Freitas M, Ribeiro D, Tomé SM, Silva AM, Fernandes E.
Abstract : Neutrophils are considered the central cells of acute inflammation. Flavonoids have been suggested as therapeutic agents to avoid damages induced by inflammatory processes. It is well known the reactivity of flavonoids with hypochlorous acid produced by neutrophils, to form stable mono and dichlorinated products. In this study, we synthesized novel chlorinated flavonoids and investigated their effect in neutrophils' oxidative burst and in its lifespan, in comparison with the parent non-chlorinated flavonoids. The obtained results demonstrate that chlorinated flavonoids were more efficient than their parent compounds in modulating neutrophils' oxidative burst in phorbol myristate acetate-activated neutrophils. Some of the tested flavonoids drive neutrophil apoptosis in a caspase 3-dependent fashion. The present data showed that 8-chloro-3',4',5,7-tetrahydroxyflavone (4a) constitute an alternative anti-inflammatory therapy, due to the proven ability to suppress mechanisms engaged at the onset and progression of inflammation.
|
Inhibition of PMA-induced oxidative burst in human neutrophils at 50 uM by amplex red assay
|
Homo sapiens
|
40.0
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis of chlorinated flavonoids with anti-inflammatory and pro-apoptotic activities in human neutrophils.
Year : 2014
Volume : 86
First Page : 153
Last Page : 164
Authors : Freitas M, Ribeiro D, Tomé SM, Silva AM, Fernandes E.
Abstract : Neutrophils are considered the central cells of acute inflammation. Flavonoids have been suggested as therapeutic agents to avoid damages induced by inflammatory processes. It is well known the reactivity of flavonoids with hypochlorous acid produced by neutrophils, to form stable mono and dichlorinated products. In this study, we synthesized novel chlorinated flavonoids and investigated their effect in neutrophils' oxidative burst and in its lifespan, in comparison with the parent non-chlorinated flavonoids. The obtained results demonstrate that chlorinated flavonoids were more efficient than their parent compounds in modulating neutrophils' oxidative burst in phorbol myristate acetate-activated neutrophils. Some of the tested flavonoids drive neutrophil apoptosis in a caspase 3-dependent fashion. The present data showed that 8-chloro-3',4',5,7-tetrahydroxyflavone (4a) constitute an alternative anti-inflammatory therapy, due to the proven ability to suppress mechanisms engaged at the onset and progression of inflammation.
|
Inhibition of PMA-induced oxidative burst in human neutrophils at 50 uM by APF assay
|
Homo sapiens
|
40.0
%
|
|
Journal : Eur. J. Med. Chem.
Title : Synthesis of chlorinated flavonoids with anti-inflammatory and pro-apoptotic activities in human neutrophils.
Year : 2014
Volume : 86
First Page : 153
Last Page : 164
Authors : Freitas M, Ribeiro D, Tomé SM, Silva AM, Fernandes E.
Abstract : Neutrophils are considered the central cells of acute inflammation. Flavonoids have been suggested as therapeutic agents to avoid damages induced by inflammatory processes. It is well known the reactivity of flavonoids with hypochlorous acid produced by neutrophils, to form stable mono and dichlorinated products. In this study, we synthesized novel chlorinated flavonoids and investigated their effect in neutrophils' oxidative burst and in its lifespan, in comparison with the parent non-chlorinated flavonoids. The obtained results demonstrate that chlorinated flavonoids were more efficient than their parent compounds in modulating neutrophils' oxidative burst in phorbol myristate acetate-activated neutrophils. Some of the tested flavonoids drive neutrophil apoptosis in a caspase 3-dependent fashion. The present data showed that 8-chloro-3',4',5,7-tetrahydroxyflavone (4a) constitute an alternative anti-inflammatory therapy, due to the proven ability to suppress mechanisms engaged at the onset and progression of inflammation.
|
Inhibition of sucrose loaded POPC/POPE/POPS/PtdIns(3,4,5)P3 (59:20:20:1) liposome binding to eGFP-fused PDK1 PH domain (unknown origin) expressed in Escherichia coli BL21 at 20 uM after 10 mins by fluorescence spectrophotometry based pull down assay relative to control
|
Homo sapiens
|
-1.93
%
|
|
Journal : Bioorg Med Chem Lett
Title : Inhibitory potential of flavonoids on PtdIns(3,4,5)P3 binding with the phosphoinositide-dependent kinase 1 pleckstrin homology domain.
Year : 2017
Volume : 27
Issue : 3
First Page : 420
Last Page : 426
Authors : Kang Y, Kim BG, Kim S, Lee Y, Yoon Y.
Abstract : Many membrane-associated proteins are involved in various signaling pathways, including the phosphoinositide 3-kinase (PI3K) pathway, which has key roles in diverse cellular processes. Disruption of the activities of these proteins is involved in the development of disease in humans, making these proteins promising targets for drug development. In most cases, the catalytic domain is targeted; however, it is also possible to target membrane associations in order to regulate protein activity. In this study, we established a novel method to study protein-lipid interactions and screened for flavonoid-derived antagonists of PtdIns(3,4,5)P3 binding with the phosphoinositide-dependent kinase 1 (PDK1) pleckstrin homology (PH) domain. Using an enhanced green fluorescent protein (eGFP)-tagged PDK1 PH domain and 50% sucrose-loaded liposomes, the protein-lipid interaction could be efficiently evaluated using liposome pull-down assays coupled with fluorescence spectrophotometry, and a total of 32 flavonoids were screened as antagonists for PtdIns(3,4,5)P3 binding with the PDK1 PH domain. From this analysis, we found that two adjunct hydroxyl groups in the C ring were responsible for the inhibitory effects of the flavonoids. Because the flavonoids shared structural similarities, the results were then subjected to quantitative structure-activity relationship (QSAR) analysis. The results were then further confirmed by in silico docking experiments. Taken together, our strategy presented herein to screen antagonists targeting lipid-protein interactions could be an alternative method for identification and characterization of drug candidates.
|
Antiinflammatory activity in mouse RAW264.7 cells assessed as inhibition of LPS-stimulated NO production at 20 uM by ELISA relative to control
|
Mus musculus
|
16.33
%
|
|
Journal : Bioorg Med Chem Lett
Title : Identification and structure activity relationship of novel flavone derivatives that inhibit the production of nitric oxide and PGE2 in LPS-induced RAW 264.7 cells.
Year : 2017
Volume : 27
Issue : 11
First Page : 2613
Last Page : 2616
Authors : An JY, Lee HH, Shin JS, Yoo HS, Park JS, Son SH, Kim SW, Yu J, Lee J, Lee KT, Kim NJ.
Abstract : In an effort to identify novel anti-inflammatory compounds, a series of flavone derivatives were synthesized and biologically evaluated for their inhibitory effects on the production of nitric oxide (NO) and prostaglandin E2 (PGE2), representative pro-inflammatory mediators, in LPS-induced RAW 264.7 cells. Their structure-activity relationship was also investigated. In particular, we found that compound 3g displayed more potent inhibitory activities on PGE2 production, similar inhibitory activities on NO production and less weak cytotoxicity than luteolin, a natural flavone known as a potent anti-inflammatory agent.
|
Inhibition of human CYP1B1 expressed in Escherichia coli DH5alpha coexpressing human NADPH P450 reductase using 7-ethoxyresorufin as substrate in presence of NADP+ by spectrofluorometeric analysis
|
Homo sapiens
|
600.0
nM
|
|
Journal : Eur J Med Chem
Title : Inhibitors of cytochrome P450 (CYP) 1B1.
Year : 2017
Volume : 135
First Page : 296
Last Page : 306
Authors : Dutour R, Poirier D.
Abstract : Human cytochrome P450 1B1 (CYP1B1) is involved in the metabolism of various drugs. This enzyme catalyzes the hydroxylation of aryl compounds, thus generating more polar metabolites that can be easily excreted. CYP1B1 is also known for its ability to activate procarcinogens into carcinogens. For example, it can hydroxylate 17β-estradiol (E2) into 4-hydroxy-E2, which can promote tumorigenesis as a potent estrogen, or after being transformed into E2-3,4-quinone. Since elevated expression levels of CYP1B1 have been reported in various cancers, but not in normal tissues, this enzyme represents an interesting therapeutic target. This review put emphasis on different families of inhibitors, especially those reported since 2003.
|
Inhibition of DPP4 (unknown origin) using Gly-Pro-AMC as substrate preincubated for 4 secs followed by substrate addition and measured after 30 mins by luminescence assay
|
Homo sapiens
|
170.0
nM
|
|
Journal : Eur J Med Chem
Title : Recent progress of the development of dipeptidyl peptidase-4 inhibitors for the treatment of type 2 diabetes mellitus.
Year : 2018
Volume : 151
First Page : 145
Last Page : 157
Authors : Li N, Wang LJ, Jiang B, Li XQ, Guo CL, Guo SJ, Shi DY.
Abstract : Diabetes is a fast growing chronic metabolic disorder around the world. Dipeptidyl peptidase-4 (DPP-4) is a new promising target during type 2 diabetes glycemic control. Thus, a number of potent DPP-4 inhibitors were developed and play a rapidly evolving role in the management of type 2 diabetes in recent years. This article reviews the development of synthetic and natural DPP-4 inhibitors from 2012 to 2017 and provides their physico-chemical properties, biological activities against DPP-4 and selectivity over dipeptidyl peptidase-8/9. Moreover, the glucose-lowering mechanisms and the active site of DPP-4 are also discussed. We also discuss strategies and structure-activity relationships for identifying potent DPP-4 inhibitors, which will provide useful information for developing potent DPP-4 drugs as type 2 diabtes treatments.
|
Inhibition of human liver FBP1 at 200 uM incubated for 5 mins by fluorescence method relative to control
|
Homo sapiens
|
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.
|
Inhibition of cytochrome c (unknown origin) assessed as reduction in cyt c-CL complex formation at 10 uM incubated for 15 mins in presence of cardiolipin by Trp-59 fluorescence assay relative to control
|
Homo sapiens
|
87.0
%
|
|
Journal : Bioorg Med Chem
Title : A role of flavonoids in cytochrome c-cardiolipin interactions.
Year : 2021
Volume : 33
First Page : 116043
Last Page : 116043
Authors : Rice M,Wong B,Oja M,Samuels K,Williams AK,Fong J,Sapse AM,Maran U,Korobkova EA
Abstract : The processes preceding the detachment of cytochrome c (cyt c) from the inner mitochondrial membrane in intrinsic apoptosis involve peroxidation of cardiolipin (CL) catalyzed by cyt c-CL complex. In the present work, we studied the effect of 17 dietary flavonoids on the peroxidase activity of cyt c bound to liposomes. Specifically, we explored the relationship between peroxidase activity and flavonoids' (1) potential to modulate cyt c unfolding, (2) effect on the oxidation state of heme iron, (3) membrane permeability, (4) membrane binding energy, and (5) structure. The measurements revealed that flavones, flavonols, and flavanols were the strongest, while isoflavones were the weakest inhibitors of the oxidation. Flavonoids' peroxidase inhibition activity correlated positively with their potential to suppress Trp-59 fluorescence in cyt c as well as the number of OH groups. Hydrophilic flavonoids, such as catechin, having the lowest membrane permeability and the strongest binding with phosphocholine (PC) based on the quantum chemical calculations exhibited the strongest inhibition of Amplex Red (AR) peroxidation, suggesting a membrane-protective function of flavonoids at the surface. The results of the present research specify basic principles for the design of molecules that will control the catalytic oxidation of lipids in mitochondrial membranes. These principles take into account the number of hydroxyl groups and hydrophilicity of flavonoids.
|
Inhibition of cytochrome c (unknown origin) assessed as reduction in cyt c-CL peroxidase activity at 10 uM up to 20 mins in presence of cardiolipin by Amplex red staining based fluorescence assay relative to control
|
Homo sapiens
|
50.0
%
|
|
Journal : Bioorg Med Chem
Title : A role of flavonoids in cytochrome c-cardiolipin interactions.
Year : 2021
Volume : 33
First Page : 116043
Last Page : 116043
Authors : Rice M,Wong B,Oja M,Samuels K,Williams AK,Fong J,Sapse AM,Maran U,Korobkova EA
Abstract : The processes preceding the detachment of cytochrome c (cyt c) from the inner mitochondrial membrane in intrinsic apoptosis involve peroxidation of cardiolipin (CL) catalyzed by cyt c-CL complex. In the present work, we studied the effect of 17 dietary flavonoids on the peroxidase activity of cyt c bound to liposomes. Specifically, we explored the relationship between peroxidase activity and flavonoids' (1) potential to modulate cyt c unfolding, (2) effect on the oxidation state of heme iron, (3) membrane permeability, (4) membrane binding energy, and (5) structure. The measurements revealed that flavones, flavonols, and flavanols were the strongest, while isoflavones were the weakest inhibitors of the oxidation. Flavonoids' peroxidase inhibition activity correlated positively with their potential to suppress Trp-59 fluorescence in cyt c as well as the number of OH groups. Hydrophilic flavonoids, such as catechin, having the lowest membrane permeability and the strongest binding with phosphocholine (PC) based on the quantum chemical calculations exhibited the strongest inhibition of Amplex Red (AR) peroxidation, suggesting a membrane-protective function of flavonoids at the surface. The results of the present research specify basic principles for the design of molecules that will control the catalytic oxidation of lipids in mitochondrial membranes. These principles take into account the number of hydroxyl groups and hydrophilicity of flavonoids.
|
Inhibition of cytochrome c (unknown origin) assessed as reduction reduction of cyt c from its ferric state to ferrous state at 10 uM incubated for 20 mins in presence of cardiolipin by UV-vis Spectrophotometric assay relative to control
|
Homo sapiens
|
0.0
%
|
|
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.
