Computer-aided design of selective Cytochrome P450 inhibitors and docking studies of alkyl resorcinol derivatives

The present investigation is aimed to understand the interactive mechanism that occurs between the active site of Cytochrome P450 and its inhibitors by molecular modeling studies. Based on the docking studies and information obtained from interaction analysis, structure-based virtual screening was performed by selecting 217 new potential inhibitors with structural diversity using GOLD and ArgusLab molecular docking softwares. Among a total of 217 compounds, only 21 molecules were considered as the potential inhibitors. Hydrogen bond and van der Waals interaction between various active site residues like ARG 382, HIS447, CYS449, ASN493, TYR131, and TYR92 of Cytochrome P450 were observed. Docking studies of selected resorcinols showed an optimal molecular environment which is required to bind with active sites of Cytochrome P450. Hydroxyl groups of resorcinols exhibited van der Waals interactions with certain active sites. To estimate the drug-likeness properties the parameters like partition coefficient (log P), tabulated molecular polar surface area (TPSA), and bio activity score were obtained from the Molinspiration studies. Based on docking and Molinspiration data analysis, the molecules 10, 3, 18, 19, and 7 were found to be highly potent inhibitors of Cytochrome P450.