SAR and QSAR of the Antioxidant Activity of Flavonoids (original) (raw)
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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.
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. .
Bioorganic & Medicinal Chemistry, 2007
Quantitative structure-activity relationship (QSAR) models are useful in understanding how chemical structure relates to the biological activity of natural and synthetic chemicals and for design of newer and better therapeutics. In the present study, 46 flavonoids and related polyphenols were evaluated for direct/indirect antioxidant activity in three different assay systems of increasing complexity (chemical, enzymatic, and intact phagocytes). Based on these data, two different QSAR models were developed using i) physicochemical and structural (PC&S) descriptors to generate multiparameter partial least squares (PLS) regression equations derived from optimized molecular structures of the tested compounds and ii) a partial 3D comparison of the 46 compounds with local fingerprints obtained from fragments of the molecules by the frontal polygon (FP) method. We obtained much higher QSAR correlation coefficients (r) for flavonoid end-point antioxidant activity in all 3 assay systems using the FP method (0.966, 0.948, and 0.965 for datasets in evaluated in the biochemical, enzymatic, and whole cells assay systems, respectively). Furthermore, high leave-oneout cross-validation coefficients (q 2 ) of 0.907, 0.821, and 0.897 for these datasets, respectively, indicated enhanced predictive ability and robustness of the model. Using the FP method, structural fragments (submolecules) responsible for the end-point antioxidant activity in the three assay systems were also identified. To our knowledge, this is the first QSAR model derived for description of flavonoid direct/indirect antioxidant effects in a cellular system, and this model could form the basis for further drug development of flavonoid-like antioxidant compounds with therapeutic potential.
Study of Radical Scavenging Activities of a Series of Flavonoids through 3D-QSAR Analysis
Asian Journal of Chemistry, 2018
Free radicals are the spontaneous outcome of metabolic processes in all living beings and are considered to be the main cause behind cell death and ageing [1]. Free radicals are very much unstable and highly reactive leading to unwanted electron transfer, proton transfer, H-atom abstraction or addition which harm various organs and tissues of living being. Oxy radicals have been found to be responsible for diseases like rheumatoid arthritis, cancer, inflammation, coronary heart disease, diabetes, Parkinson's disease, cystic fibrosis, Alzheimer's disease and many others [2-8]. Antioxidants are mostly naturally occurring substances, abundant in fruits and vegetables. These are broadly classified into three classes depending on their action (a) as scavangers, (b) metal chelators and (c) as enzyme inhibitors [9,10]. Whereas scavenging type antioxidants directly removes radicals, two other types of antioxidants prevent the generation of radicals indirectly. The scavenging type antioxidants have received most attention due to their direct mode of action [11]. Flavonoids are multiple-OH containing molecules found in various natural sources like fruits, vegetables, tea, wine, etc. These molecules are present in various parts of plants like stems, bark, roots, grains and even in flowers [12-15]. Intake
Quantitative Structure – Antioxidant Activity Relationships of Flavonoid Compounds
Molecules, 2004
A quantitative structure -antioxidant activity relationship (QSAR) study of 36 flavonoids was performed using the partial least squares projection of latent structures (PLS) method. The chemical structures of the flavonoids have been characterized by constitutional descriptors, two-dimensional topological and connectivity indices. Our PLS model gave a proper description and a suitable prediction of the antioxidant activities of a diverse set of flavonoids having clustering tendency.
Revista de Chimie
Using different methods of statistics, this paper aims to highlight the potential link between the antioxidant activity of flavonoids and the corresponding molecular descriptors. By calculating the descriptors (van der Waals surface (A), molar volume (V), partition coefficient (LogP), refractivity (R), polarizability (a), forming heat (Hformation), hydration energy (Ehidr), the dipole moment (mt)), together with antioxidant activities (RSA) calculated or taken from the literature, number of phenolic -OH groups and the presence (2) or absence (1) of C2=C3 double bond) for 29 flavonoid compounds and by intercorrelation between the studied parameters, the link between the number of phenolic groups grafted to the basic structure of flavonoids and their antioxidant activity was confirmed. Simultaneously, by using the chi-squared test and the intercorrelations matrix, a satisfactorily correlation coefficient (r2=0.5678; r=0.7536) between the structure of the flavonoids and their activity ...
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.
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.