Protection of Flavonoids Against Lipid Peroxidation: The Structure Activity Relationship Revisited (original) (raw)
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Antioxidant properties of hydroxy-flavones
Free Radical Biology and Medicine, 1996
The antioxidant properties of 24 hydroxy-flavones were evaluated. Results show that 2',3 ',4'-OH substitution on the B ring plays a crucial role in radical scavenger activity in the DPPH assay and in the inhibitory effect on pereoxydation of tissue lipids in the MDA test. The formation of stable radicals for this type of compounds has been studied by ESR. In addition, it has been found that 7-hydroxy-flavones are potent competitive inhibitors of xanthine oxidase. It is proposed that the C-7 OH of flavones may take the place of the C-2 or C-6 OH of xanthine in the active site of the enzyme. A C-4' OH or C-4' OMe substitution on the 7-hydroxy flavones is not favourable to a fit in the active site. The 2',3 ',4'-trihydroxy-flavones inhibited XO by another process, which remains to be determined. In summary, this study provides evidence that hydroxy-flavones exhibit interesting antioxidant properties expressed either by the capacity to scavenge free radicals (for 2',3 ',4'-trihydroxy-flavones) or to competitively inhibit xanthine oxidase (for 7-hydroxy-flavones). These compounds may be drug candidates for treating pathologies related to free radical oxidation.
Biochemical Pharmacology, 1990
Polymethoxylated flavones and C-glycosyl derivatives isolated from medicinal plants besides other flavonoid compounds were studied for their influence on lipid peroxidation induced by FeSO,+cysteine in rat liver microsomes. A number of hydroxytlavones (e.g. luteolin); C-glycosylflavones (e.g. orientin); methoxyflavones (e.g. gardenin D) and flavonols (e.g. datiscetin), as well as the flavanol leucocyanidol and the biflavone amentoflavone behaved as inhibitors of non-enzymic lipid peroxidation. Structure-activity relationships were established and it was observed that the structural features for active polyhydroxylated compounds were different from those of polymethoxylated flavones, antiperoxidative flavonoids possessing a high lipophilicity.
On the antioxidant properties of three synthetic flavonols
Die Pharmazie, 2007
The antioxidant properties of a series of synthetic and natural flavonoids towards the oxygenated species superoxide radical anion (O 2 .-) enzimatically generated, were evaluated. 7-Hydroxyflavonol, 7,3 0-dihydroxyflavonol and 3 0-hydroxyflavonol were synthesised, with a systematic variation of the OH substitution on positions C3, C7, C3 0 and C4 0 , and their respective antioxidative abilities compared to those of the already characterised natural flavonoids quercetin, kaempferol and rutin. The efficiency of O 2 .-deactivation by the flavonoids does not correlate with their respective determined oxidation potentials, suggesting that the pure one-electron-transfer-mechanism of O 2 .-quenching could not be the main scavenging process involved. Experimental evidence demonstrated that the possible inhibition of the O 2 .-generator enzymatic system by the flavonoids must be disregarded as a possible indirect cause for the inhibition of the oxidative species. One possible mechanism for the inhibition of O 2 .-, highly dependent on the substitution pattern of the flavonoid, may be the generation of hydroperoxides or dioxetanes as oxidation products, as already postulated for other biologically relevant compounds. The simultaneous OH-substitution on positions C3 and C7 of the flavonoid skeleton plays a definitive role in the enhancement of the O 2 .-inhibitory effect. The replacement of OH by a O-rutinosyl group on position C7 suppresses at all that effect, whereas the absence of an OH group in position 7 significantly reduces the antioxidative power. Finally, the presence of OH groups on positions 3 0 and 4 0 does not produce any determinant effect in the antioxidative behaviour of the flavonoids.
ChemInform, 2001
A series of 3,7-disubstituted-2-(3′,4′-dihydroxyphenyl)flavones was synthesized as potential cardioprotective agents in doxorubicin antitumor therapy. The influence of substituents on the 3 and 7 positions of the flavone nucleus on radical scavenging and antioxidant properties was explored to improve the antioxidant activity of our lead compound monoHER. In the TEAC assay most compounds had a similar potency (3.5-5 times as potent as trolox), but in the LPO assay IC 50 values ranged from 0.2 to 37 µM. In general, the 3-substituted flavones (9a-j) were the most potent compounds in the LPO assay. The number of hydroxyl groups is not the only prerequisite for antioxidant activity. Substitution in ring A of the flavonoid is not necessary for high activity, but the presence of a 7-OH group significantly modifies the antioxidant activity. The compounds are good antioxidants, which makes it interesting to evaluate them as cardioprotective agents. a Yield determined from intermediate to product. b Fisetin. c van den Berg, R.; Haenen, G. R. M. M.; van den Berg, H.; van der Vijgh, W. J. F.; Bast, A. The predictive value of the antioxidant capacity of structurally related flavonoids using the trolox equivalent antioxidant capacity (TEAC) assay.
Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships
The Journal of Nutritional Biochemistry, 2002
Flavonoids are a class of secondary plant phenolics with significant antioxidant and chelating properties. In the human diet, they are most concentrated in fruits, vegetables, wines, teas and cocoa. Their cardioprotective effects stem from the ability to inhibit lipid peroxidation, chelate redox-active metals, and attenuate other processes involving reactive oxygen species. Flavonoids occur in foods primarily as glycosides and polymers that are degraded to variable extents in the digestive tract. Although metabolism of these compounds remains elusive, enteric absorption occurs sufficiently to reduce plasma indices of oxidant status. The propensity of a flavonoid to inhibit free-radical mediated events is governed by its chemical structure. Since these compounds are based on the flavan nucleus, the number, positions, and types of substitutions influence radical scavenging and chelating activity. The diversity and multiple mechanisms of flavonoid action, together with the numerous methods of initiation, detection and measurement of oxidative processes in vitro and in vivo offer plausible explanations for existing discrepancies in structure-activity relationships. Despite some inconsistent lines of evidence, several structureactivity relationships are well established in vitro. Multiple hydroxyl groups confer upon the molecule substantial antioxidant, chelating and prooxidant activity. Methoxy groups introduce unfavorable steric effects and increase lipophilicity and membrane partitioning. A double bond and carbonyl function in the heterocycle or polymerization of the nuclear structure increases activity by affording a more stable flavonoid radical through conjugation and electron delocalization. Further investigation of the metabolism of these phytochemicals is justified to extend structure-activity relationships (SAR) to preventive and therapeutic nutritional strategies. .
Journal of Medicinal Chemistry, 2000
A series of 3,7-disubstituted-2-(3′,4′-dihydroxyphenyl)flavones was synthesized as potential cardioprotective agents in doxorubicin antitumor therapy. The influence of substituents on the 3 and 7 positions of the flavone nucleus on radical scavenging and antioxidant properties was explored to improve the antioxidant activity of our lead compound monoHER. In the TEAC assay most compounds had a similar potency (3.5-5 times as potent as trolox), but in the LPO assay IC 50 values ranged from 0.2 to 37 µM. In general, the 3-substituted flavones (9a-j) were the most potent compounds in the LPO assay. The number of hydroxyl groups is not the only prerequisite for antioxidant activity. Substitution in ring A of the flavonoid is not necessary for high activity, but the presence of a 7-OH group significantly modifies the antioxidant activity. The compounds are good antioxidants, which makes it interesting to evaluate them as cardioprotective agents. a Yield determined from intermediate to product. b Fisetin. c van den Berg, R.; Haenen, G. R. M. M.; van den Berg, H.; van der Vijgh, W. J. F.; Bast, A. The predictive value of the antioxidant capacity of structurally related flavonoids using the trolox equivalent antioxidant capacity (TEAC) assay.
Medicinal Chemistry Research, 2019
DFT calculations were performed on nine flavones and flavonols to explain their high antioxidant activity and variations in their activity. Conformational analysis showed that only flavonols with 3-OH directed toward the Bring are nonplanar; however, flavones and resulted radicals are planar. Hydroxyl group eligible for dissociation is the one with ortho OH directed toward it; otherwise, one of Bring (in 2′ or 4′-position) hydroxyl group. There are two main factors responsible for stabilizing the resulted radicals and lowering the bond dissociation energy and hence there were found well correlated with the experimental activity. First, driving force resulted from the conversion of nonplanar flavonols to planar radicals accompanied by resonance toward the carbonyl group and H-bond formation with 3-OH and second, radical stabilization by H-bond with ortho hydroxyl group with resonance toward carbonyl or pyrone oxygen. All resonance and H-bonds were confirmed by spin density, bond length, and molecular orbital calculations.
Antioxidant properties of flavonoids
Abstrak Flavonoids, metabolit sekunder terbanyak yang bersumber dari tanaman, telah lama dimanfaatkan sebagai obat tradisional dan secara ilmiah juga telah terbukti memiliki efek farmakologi. Senyawa ini juga memiliki beragam manfaat terhadap kesehatan sehingga sangat berpotensi sebagai bahan baku untuk pengembangan obat baru. Penelitian terbaru memaparkan pemanfaatan flavonoids sebagai antioksidan untuk penyakit akibat radikal bebas. Sari pustaka ini menyoroti peran flavonoid sebagai anti oksidan. Abstract Flavonoids represent a remarkable group of plant secondary metabolites and have long been used as traditional medicines with scientifically proven pharmacological benefits. They serve vast-ranging medicinal activities that may lead drug discovery with novel and potential therapeutic evidence. Latest research magnifies primarily functional activity of flavonoids as antioxidant against oxidative stress. This review enlightens the prospective role of flavonoids as antioxidant.
Flavonoids as superoxide scavengers and antioxidants
Free Radical Biology and Medicine, 1990
The superoxide anions scavenging activity and antioxidation of seven flavonoids-quercetin, rutin, morin, acacetin, hispidulin, hesperidin, and naringin-were studied. The superoxide anions were generated in a phenazin methosulphate-NADH system and were assayed by reduction of nitroblue tetrazolium. The scavenging activity ranked: rutin was the strongest, and quercetin and naringin the second, while morin and hispidulin were very weak. The concentration values yielding 50% inhibition of lipid peroxidation in mouse liver homogenate were in order of 10-6 M for quercetin, rutin, and morin; and of 10-5 M for acacetin and hispidulin, while naringin and hesperidin had no antioxidative action. In comparison with the antioxidative and scavenging activities of flavonoids, there are no correlations.
Prooxidant character of flavonoid cytotoxicity: Structure-activity relationships
Iubmb Life, 1998
The action of flavonoids on bovine leukemia virus-transformed lamb fibroblasts (line FLK) and HL-60 cells was accompanied by lipid peroxidation, their toxicity was partly prevented by iron chelator desferrioxamine and antioxidant N,N'-diphenyl-p-phenylene diamine. This pointed out to the involvement of oxidative stress in flavonoid cytotoxicity. The concentration of compound for 50% survival of FLK cells (cL 50) did not show correlation with polarographic oxidation half-peak potential (Ep/2) and/or partition coefficient (log P) of flavonoids; however, their toxicity to HL-60 cells was described by equation log cL 50 (μΜ) = 3.0161 + 1.1099 E p/2 (V)-0.3369 log P. The toxicity of quercetin was partly prevented by nontoxic concentrations of other flavonoids examined, thus pointing out to potential neutralization of quercetin cytotoxicity by intake of flavonoid mixtures.