In Vitro Inhibition of Human Placental Glutathione S-Transferase by 3-Arylcoumarin Derivatives


ALPARSLAN M. M. , DANIŞ Ö.

ARCHIV DER PHARMAZIE, vol.348, no.9, pp.635-642, 2015 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 348 Issue: 9
  • Publication Date: 2015
  • Doi Number: 10.1002/ardp.201500151
  • Journal Name: ARCHIV DER PHARMAZIE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.635-642
  • Keywords: Arylcoumarin, Glutathione S-transferase, GSTP1-1, Multidrug resistance, CHROMENONE-CROWN-ETHERS, DRUG-RESISTANCE, STRUCTURAL REQUIREMENTS, P1-1, COUMARIN, ACID, PI, METABOLITES, ESCULETIN, APOPTOSIS
  • Marmara University Affiliated: Yes

Abstract

Glutathione S-transferases (EC: 2.5.1.18, GSTs) are phase II detoxification enzymes that catalyze the conjugation of various electrophilic compounds to glutathione (GSH), thus usually producing less reactive and more water soluble compounds. However, there is evidence that elevated expression of GSTs, especially GSTP1, is involved in the resistance of tumor cells against chemotherapeutic agents. In this study, we synthesized and investigated the inhibitory effects of differently substituted 3-arylcoumarin derivatives on human placental GST, identified as GSTP1-1, using 1-chloro-2,4-dinitrobenzene as a substrate. A known potent inhibitor of GST, ethacrynic acid was used as a positive control. Among the tested compounds, 6,7-dihydroxy substituted coumarin derivatives exhibited the highest inhibitory activity (IC50=13.50-20.83M). These results suggest that 6,7-dihydroxy-3-arylcoumarins may represent a new promising scaffold to discover potent GST inhibitors.