Potent inhibitors of equine steroid isomerase EcaGST A3-3

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Lindstrom H., Mazari A. M. A., Musdal Y., Mannervik B.

PLOS ONE, cilt.14, sa.3, 2019 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 14 Sayı: 3
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1371/journal.pone.0214160
  • Dergi Adı: PLOS ONE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Hacettepe Üniversitesi Adresli: Hayır

Özet

Equine glutathione transferase A3-3 (EcaGST A3-3) belongs to the superfamily of detoxication enzymes found in all higher organisms. However, it is also the most efficient steroid double-bond isomerase known in mammals. Equus ferus caballus shares the steroidogenic pathway with Homo sapiens, which makes the horse a suitable animal model for investigations of human steroidogenesis. Inhibition of the enzyme has potential for treatment of steroid-hormone-dependent disorders. Screening of a library of FDA-approved drugs identified 16 out of 1040 compounds, which at 10 mu M concentration afforded at least 50% inhibition of EcaGST A3-3. The most potent inhibitors, anthralin, sennoside A, tannic acid, and ethacrynic acid, were characterized by IC50 values in the submicromolar range when assayed with the natural substrate Delta(5)-androstene-3,17-dione.