Mechanistic insight into the radical scavenging activity of polyphenols and its application in virtual screening of phytochemical library: an in silico approach

Abstract

Polyphenols are amply present in fruits, vegetables, beverages and thus very common items in our diet. They are better characterized as antioxidants and are able to scavenge various radicals and singlet oxygen. The present study aims to provide structural and electronic insight into the antioxidant activity of polyphenols and identify novel natural antioxidant. With systematic searches of the large descriptor spaces available in CODESSA, we found that number of benzene ring (constitutional descriptors), electrostatic descriptors related to the hydrogen bonding ability and the lowest unoccupied molecular orbital (LUMO) energy of the polyphenols are very important descriptors related to the electron donation ability of polyphenols, evident from t test values and principal component analysis. Decreasing LUMO energy facilitates electron transfer and stability of the resulting polyphenolic radical increases with the number of attached aromatic ring due to enhanced resonance. Hydrogen bonding present in the parent polyphenol also facilitates electron donation and stabilizes the phenolic radical. Using multiple linear regressions, we have derived two quantitative structure activity relation (QSAR) models with four and five descriptors, respectively, and validated using cross-validation techniques. The calculated square correlation coefficient for four and five descriptor models is R ² = 0.89 and R ² = 0.9, respectively, with cross-validated squared correlation coefficient ${R}_{\text{CV}}^{2}$  = 0.83 and ${R}_{\text{CV}}^{2}$ = 0.87, respectively. Virtual screening using the derived QSAR models on in-house developed phytochemical database identified several highly potent natural antioxidants exhibiting their activity by electron donation coupled proton transfer pathway.