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

ALPARSLAN M. M., DANIŞ Ö.

ARCHIV DER PHARMAZIE, cilt.348, sa.9, ss.635-642, 2015 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 348 Sayı: 9
  • Basım Tarihi: 2015
  • Doi Numarası: 10.1002/ardp.201500151
  • Dergi Adı: ARCHIV DER PHARMAZIE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.635-642
  • Anahtar Kelimeler: Arylcoumarin, Glutathione S-transferase, GSTP1-1, Multidrug resistance, CHROMENONE-CROWN-ETHERS, DRUG-RESISTANCE, STRUCTURAL REQUIREMENTS, P1-1, COUMARIN, ACID, PI, METABOLITES, ESCULETIN, APOPTOSIS
  • Marmara Üniversitesi Adresli: Evet

Özet

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.