Pharmacophore-Based Virtual Screening of Novel GSTP1-1 Inhibitors

Yıl 2018, Cilt: 5 Sayı: 3, 1279 - 1286, 01.09.2018

Kayhan Bolelli Tugba Ertan-bolelli

https://doi.org/10.18596/jotcsa.466458

Cited By: 1

Öz

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.

Anahtar Kelimeler

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

Kaynakça

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