Pharmacophore-Based Virtual Screening of Novel GSTP1-1 Inhibitors

Abstract

Glutathione transferase enzymes play an important role in metabolism and detoxification of numerous xenobiotics, electrophilic drugs, environmental carcinogens, and products of oxidative stress in living organisms. Human GST P1-1 is the most prevalent isoform of the mammalian cytosolic GSTs and this enzyme participates in a particular role in one of the mechanisms of the development of resistance in cancer cells toward the administration of anticancer agents in chemotherapy.

Herein, pharmacophore analysis were performed using bioactive conformation of the known inhibitor of GSTP1-1, ethacrynic acid (pdb ID:2GSS). Phase module of the Schrödinger suite was used to generate pharmacophore hypothesis. Molecules with same pharmacophoric features were screened from among the commercially available compounds in the ZINC database and ligand filtration was also done to obtain an efficient collection of hit molecules by employing Lipinski “rule of five” using Qikprop module. As a result, some of the compounds obtained from this study, could be the promising inhibitors of hGSTP1-1 enzyme.

Keywords

• ADME/Tox,drug resistance,GSTP1-1,pharmacophore analysis,virtual screening

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