Inhibition of cytochrome P450 3A by acetoxylated analogues of resveratrol in in vitro and in silico models.

ABSTRACT: Many dietary compounds, including resveratrol, are potent inhibitors of CYP3A4. Here we examined the potential to predict inhibition capacity of dietary polyphenolics using an in silico and in vitro approaches and synthetic model compounds. Mono, di, and tri-acetoxy resveratrol were synthesized, a cell line of human intestine origin and microsomes from rat liver served to determine their in vitro inhibition of CYP3A4, and compared to that of resveratrol. Docking simulation served to predict the affinity of the synthetic model compounds to the enzyme. Modelling of the enzyme's binding site revealed three types of interaction: hydrophobic, electrostatic and H-bonding. The simulation revealed that each of the examined acetylations of resveratrol led to the loss of important interactions of al

SUBMITTER: Basheer L 

PROVIDER: S-EPMC4987671 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature