Title of article :
Improved quantitative structure–activity relationship models to predict antioxidant activity of flavonoids in chemical, enzymatic, and cellular systems Original Research Article
Author/Authors :
Andrei I. Khlebnikov، نويسنده , , Igor A. Schepetkin، نويسنده , , Nina G. Domina، نويسنده , , Liliya N. Kirpotina، نويسنده , , Mark T. Quinn، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2007
Pages :
22
From page :
1749
To page :
1770
Abstract :
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 three assay systems using the FP method (0.966, 0.948, and 0.965 for datasets evaluated in the biochemical, enzymatic, and whole cell assay systems, respectively). Furthermore, high leave-one-out cross-validation coefficients (q2) 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.
Keywords :
Flavonoids , Phagocytes , Reactive oxygen species , Antioxidants , Quantitative structure–activity relationship analysis , Molecular descriptors , Frontal polygons , drug design
Journal title :
Bioorganic and Medicinal Chemistry
Serial Year :
2007
Journal title :
Bioorganic and Medicinal Chemistry
Record number :
1305385
Link To Document :
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