Binding Models of Polyphenols to Cytochrome P450 2C9: A Molecular Docking Study

摘要

Polyphenols are widely presented in plants and dietary supplements. The beneficial effects of these compounds have been demonstrated, including the prevention of cardiovascular diseases, osteoporosis, neurogenerative diseases and diabetes. From previous studies, polyphenols showed the inhibitory effect on cytochrome P450 2C9 (CYP2C9) resulting in clinically significant of herb-drug interactions. CYP2C9 is involved in the biotransformation of various therapeutic drugs, including tolbutamide, phenytoin and warfarin. Co-administration of polyphenols with drugs that are metabolized through CYP2C9 can cause therapeutic failures or adverse events from the co-administered drugs. This study aimed to identify the interactions between polyphenols and CYP2C9 by using molecular docking program, CDOCKER, to calculate binding energy. Ten polyphenols used in this study were naringenin, chrysin, apigenin, luteolin, acacetin, galangin, kaempferol, quercetin, myricetin and isorhamnetin. The results showed that polyphenols can bind to the same binding site as flurbiprofen, which was used as the ligand in the X-ray crystal structure of the CYP2C9-flurbiprofen complex (1R9O) and the amino acid Phe100, Pro101, Glu104, Phe114, Leu208, Gly296, Ala297, Leu366 and Phe476 residues play a key role in the CYP2C9 active binding site.