7. Molecular modelling analysis of epigallocatechin-3-gallate

Fazlul Huq

Discipline of Biomedical Science, School of Medical Sciences, Faculty of Medicine, Cumberland Campus, C42, The University of Sydney, Lidcombe, NSW, Australia.

Phone: +61 2 9351 9522; Fax: +61 2 9351 9520 Email: F.Huq@usyd.edu.au 

Abstract

The major green tea catechin (-)-epigallocatechin-3-gallate (EGCG) is a powerful antioxidant with potent anti-inflammatory, apoptotic and cancer preventive properties. Molecular modelling analyses based on molecular mechanics, semi-empirical (PM3) and DFT (at B3LYP/6-31G* level) calculations show that EGCG and its metabolites have large LUMO-HOMO energy differences ranging from 4.5 to 5.9 eV, indicating that the compounds would be moderate to highly inert kinetically. The molecular surfaces of the compounds are found to abound in neutral green and electron-rich red and yellow regions so that they may be subject to lyophilic and electrophilic attacks. The abundance of electron-rich regions on the molecular surfaces can explain why EGCG and its metabolites would act as powerful antioxidants, thus providing an explanation for their anticarcinogenic and other propetctive roles. The molecular surfaces of EGCG and its metabolites are also found to possess a small amount of electron-deficient blue regions so that the compounds may be subject to nucleophilic attacks. Nucleophilic attacks may be due to glutathione and nucleobases in DNA as a result of which depletion of glutathione and oxidation of nucleobases in DNA may occur. The former would induce oxidative stress and hence cellular toxicity whereas the latter would cause DNA damage. However, because of kinetic inertness of the molecules and paucity of electron-deficient regions, the rates of such adverse reactions are expected to be low.
 

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