Pharmacophore-based virtual screening of novel GSTP1-1 inhibitors

Abstract

Glutathione transferase enzymes have significant role in the metabolism and detoxification of many xenobiotic, oxidative stress products, environmental carcinogens, and electrophilic drugs. Human GSTP1-1 enzyme participates in a particular role in resistance for anticancer agents in chemotherapy by overexpression. Because of these reasons this enzyme could be a promised target for new anticancer drugs. Herein, pharmacophore analysis was performed using bioactive conformation of the known inhibitor of GSTP1-1, ethacrynic acid (pdb ID:2GSS). Phase module which is available in Schrödinger software was used to generate pharmacophore hypothesis. Among the commercially available compounds in the ZINC database, with same pharmacophoric features were screened and Qikprop module was used for ligand filtration to obtain an efficient collection of hit molecules by employing Lipinski’s “rule of five”. As a result, some of the compounds obtained from this study, could be the promising inhibitors of hGSTP1-1 enzyme.