Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships (original) (raw)
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Structure-Radical Scavenging Activity Relationships of Flavonoids
Croatica Chemica Acta
The relationship between the structural characteristics of 29 flavonoids and their antiradical activity was studied. The obtained results suggest that the free radical scavenger potential of these polyphenolic compounds closely depends on the particular substitution pattern of free hydroxyl groups on the flavonoid skeleton. The possible mechanism of action of flavonoids lacking B ring OHs as free radical scavengers has been proposed.
Structure–property studies on the antioxidant activity of flavonoids present in diet
Free Radical Biology and Medicine, 2005
The screening of natural flavonoids for their bioactivity as antioxidants is usually carried out by determinination of their profile as chainbreaking antioxidants, by the evaluation of their direct free radical-scavenging activity as hydrogen-or electron-donating compounds. Since this may not be the only mechanism underlying the antioxidant activity it is important to check the ability of these compounds to act as chelators of transition metal ions. Accordingly, in the present study the acidity constants of catechin and taxifolin, as well as the formation constants of the corresponding copper (II) complexes, were investigated by potentiometry and/or spectrophotometry. Moreover, a detailed quantitative examination of the coordination species formed is presented. In addition, the partition coefficients of both catechin and taxifolin in a biomimetic system (micelles) were determined, since these properties may also contribute to the antioxidant behavior of this type of compound. The log P values determined depend on the electrostatic interactions of the compounds with the differently charged micelles (the highest values were obtained for zwitterionic and cationic micelles). The prooxidant behavior of the compounds was assessed through the oxidation of 2V-deoxyguanosine, induced by a Fenton reaction, catalyzed by copper. The data obtained reveal that the flavonoids under study did not present prooxidant activity, in this particular system. The results obtained are evidence of a clear difference among the pK a , the complexation properties, and the lipophilicity of the flavonoids studied, which can partially explain their distinct antioxidant activity. The most stable geometries of the free compounds were determined by theoretical (ab initio) methods, in order to properly account for the electron correlation effects which occur in these systems, thus allowing a better interpretation of the experimental data.
Protection of Flavonoids Against Lipid Peroxidation: The Structure Activity Relationship Revisited
Free Radical Research, 2014
The inhibition of the lipid peroxidation, induced by iron and ascorbate in rat liver microsomes, by phenols and flavones was studied. The activity of phenol was enhanced by electron donating substituents, denoted by the Hammett sigma (s ). The concentration of the substituted phenols giving 50% inhibition (IC 50 ) of lipid peroxidation gave a good correlation with the s of the substituent ðlnð1=IC 50 Þ ¼ 28:92s þ 5:80 ðR ¼ 0:94; p , 0:05ÞÞ: In flavones two pharmacophores for the protection against lipid peroxidation were pinpointed: (i) a catechol moiety as ring B and (ii) an OH-group at the 3 position with electron donating groups at the 5 and/or 7 position in the AC-ring. An example of a flavone with the latter pharmacophore is galangin (3,5,7-trihydroxyflavone) where the reactivity of the 3-OH-group is enhanced by the electron donating effect of the 5-and 7-OH-groups. This is comparable to the effect of electron donating substituents on the activity of phenol.
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.
Proceedings of the National Academy of Sciences, India Section B: Biological Sciences, 2015
The recent advances in the field of computational data production and analyses have made it easier to formulate the relationship involved between physiological properties of chemical compounds and their structures. Flavonoids are one such group of plant products that are known for exhibiting strong anti-oxidant properties owing to their radical scavenging nature. These properties establish them as important anti-cancer compounds along with being anti-bacterial, antifungal, anti-viral and anti-allergic molecules. This study aims at establishing a quantitative structure activity relationship between flavonoid structure and their anti-oxidant property. A number of molecular descriptors were calculated namely, SdsCHE-index, MMFF_2, MMFF_6, chi1, XcompDipole, T_O_O_6, MMFF_5, ?vePotentialSurfaceArea, and MMFF_29 which were chosen to build the model to elucidate crucial structural features that enhance or decrease this property. A statistically robust QSAR model was obtained with an r 2 value of 0.8765, cross validation coefficient, q 2 value of 0.7189 and pred_r 2 value of 0.5795, well above the threshold. The selected descriptors and their contribution to the regression model indicate towards the respective properties that they denote. A decrease in positively charged surface area, a high dipole moment, high number of aromatic carbon atom distribution signifies the importance of unsaturated rings, and hydroxyl groups etc. enhance the anti-oxidant activity. Thus, the present study and thus induce understanding of the structural properties of flavonoids that influence their physiological properties.
SAR and QSAR of the Antioxidant Activity of Flavonoids
Current Medicinal Chemistry, 2007
Flavonoids are a group of naturally occurring phytochemicals abundantly present in fruits, vegetables, and beverages such as wine and tea. In the past two decades, flavonoids have gained enormous interest because of their beneficial health effects such as anti-inflammatory, cardio-protective and anticancer activities. These findings have contributed to the dramatic increase in the consumption and use of dietary supplements containing high concentrations of plant flavonoids. The pharmacological effect of flavonoids is mainly due to their antioxidant activity and their inhibition of certain enzymes. In spite of abundant data, structural requirements and mechanisms underlying these effects have not been fully understood. This review presents the current knowledge about structure-activity relationships (SARs) and quantitative structure-activity relationships (QSARs) of the antioxidant activity of flavonoids. SAR and QSAR can provide useful tools for revealing the nature of flavonoid antioxidant action. They may also help in the design of new and efficient flavonoids, which could be used as potential therapeutic agents.
Flavonoids: Hemisynthesis, Reactivity, Characterization and Free Radical Scavenging Activity
Molecules, 2007
Phenolic compounds form one of the main classes of secondary metabolites. They display a large range of structures and they are responsible for the major organoleptic characteristics of plant-derived-foods and beverages, particularly color and taste properties and they also contribute to the nutritional qualities of fruits and vegetables. Phenolic compounds are also highly unstable compounds which undergo numerous enzymatic and chemical reactions during postharvest food storage and processing thus adding to the complexity of plant polyphenol composition. Among these compounds flavonoids constitute one of the most ubiquitous groups of all plant phenolics. Owing to their importance in food organoleptic properties and in human health, a better understanding of their structures, their reactivity and chemical properties in addition to the mechanisms generating them appears essential to predict and control food quality. The purpose of this work is an overview of our findings concerning the hemisynthesis, the reactivity and the enzymatic oxidation of some flavonoids and shed light on the mechanisms involved in some of these processes and the structures of the resulting products. The free radical scavenging activity of some of the synthesized compounds is also presented and a structure-activity relationship is discussed. The first part of this review concerns the synthesis and structural characterization of modified monomeric flavanols. The use of these compounds as precursor for the preparation of natural and modified dimeric Molecules 2007, 12 2229 procyanidin derivatives was then explored through different coupling reactions. The full characterization of the synthesized compounds was achieved by concerted use of NMR and ESI-MS techniques. The free radical scavenging activity of some of the synthesized compounds was investigated. The second part of this review concerns the enzymatic oxidation of several flavonols by Trametes versicolor laccase. Most of the major oxidation products have been isolated as pure compounds and their structures unambiguously established through spectroscopic methods. Correlation between the structure of the oxidation product and the substitution pattern of the starting materials allows mechanistic features of this transformation to be elucidated.
Chemistry and Biological Activities of Flavonoids: An Overview
The Scientific World Journal, 2013
There has been increasing interest in the research on flavonoids from plant sources because of their versatile health benefits reported in various epidemiological studies. Since flavonoids are directly associated with human dietary ingredients and health, there is need to evaluate structure and function relationship. The bioavailability, metabolism, and biological activity of flavonoids depend upon the configuration, total number of hydroxyl groups, and substitution of functional groups about their nuclear structure. Fruits and vegetables are the main dietary sources of flavonoids for humans, along with tea and wine. Most recent researches have focused on the health aspects of flavonoids for humans. Many flavonoids are shown to have antioxidative activity, free radical scavenging capacity, coronary heart disease prevention, hepatoprotective, anti-inflammatory, and anticancer activities, while some flavonoids exhibit potential antiviral activities. In plant systems, flavonoids help in combating oxidative stress and act as growth regulators. For pharmaceutical purposes cost-effective bulk production of different types of flavonoids has been made possible with the help of microbial biotechnology. This review highlights the structural features of flavonoids, their beneficial roles in human health, and significance in plants as well as their microbial production.
Differential effects of dietary flavonoids on drug metabolizing and antioxidant enzymes
European Journal of Cancer Prevention, 1997
This study was aimed to investigate the differential protective effect of dietary flavonoids against oxidative stress induced by proinflammatory stimuli in parenchymal liver cells. Chang Liver cells were incubated with a cytokine mixture (CM) supplemented with the flavonols quercetin and kaempferol, the flavanone taxifolin and the flavone apigenin (5-50 lM). Concentrations of oxidised and reduced glutathione, generation of different ROS/RNS, and expression of antioxidant enzymes were measured. Oxidised glutathione concentration and the oxidised/reduced glutathione ratio were increased by the CM. These effects were significantly prevented by quercetin, kaempferol and taxifolin at all tested concentrations. Effects of apigenin reached a lesser extent and were not significant at 25 lM. Treatment with quercetin and kaempferol prevented the production of peroxides, superoxide anion and nitric oxide induced by CM. Taxifolin 50 lM and apigenin 25-50 lM caused a significant increase in peroxides and nitric oxide generation. Protein concentration of the different antioxidant enzymes was generally reduced by kaempferol and quercetin in comparison to CM, although quercetin 25 and 50 lM increased Mn SOD protein concentration. GPx protein level was significantly increased by apigenin 25 and 50 lM. Changes in mRNA tended to be parallel to those in protein concentration. Our study reveals that important differences exist between flavonoids with different structural features in their capacity to abrogate the generation of different ROS/RNS, and suggests that the modulation of antioxidant enzymes by flavonoids may be also important in their antioxidant effects in liver cells.