In silico metabolism studies of dietary flavonoids by CYP1A2 and CYP2C9

Dietary flavonoids are important contributors to cancer prevention, due to their interactions with CYP family enzymes. This study describes the application of in silico tools to study the metabolism of dietary flavonoid compounds such as quercetin, rutin, naringenin and naringin, aiming to propose their potential metabolites and chemical structures and also to investigate the abilities of these compounds to interact with cytochrome P450 CYP1A2 and CYP2C9 isoforms. The reactions founded suggest that the presence of the sugar chain may account for significant change in the position of the flavonoid in the active site, due to the steric contacts. Another important finding is the participation of the amino acid residues in the metabolism. In CYP2C9, the Asn474, Ser209, Thr304 and Arg108 residues participated almost in all of the metabolically active conformations, suggesting that these residues are important for the regioselectivity and positioning of the substrate. The same was observed for the Asp313, Phe226, Phe256 and Phe260 residues of the CYP1A2 isoform. The results presented here afford new opportunities for improving the application of dietary flavonoids for the prevention of chronic disorders, as they're capable to be readily metabolized by CYP450 family.

► In silico metabolism of quercetin, rutin, naringenin and naringin was studied. ► Ligand- and structure-based approaches to improve the metabolism prediction. ► CYP1A2 and CYP2C9 complexed with the flavonoids were selected from docking. ► The results gave valuable information about the probable metabolites.