Pharmacophore-Based Virtual Screening of Novel GSTP1-1 Inhibitors

Abstract

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