Indole-Based Hydrazones Containing A Sulfonamide Moiety as Selective Inhibitors of Tumor-Associated Human Carbonic Anhydrase Isoforms IX and XII

Demir-Yazici K., Bua S., Akgunes N. M., Akdemir A., Supuran C. T., Guzel-Akdemir O.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, cilt.20, 2019 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 20
  • Basım Tarihi: 2019
  • Doi Numarası: 10.3390/ijms20092354
  • Dergi Adı: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Anahtar Kelimeler: carbonic anhydrase, sulfonamides, hydrazones, enzyme inhibition, molecular modeling, MAMMALIAN ISOFORMS, DRUG DISCOVERY, DESIGN, SOLUBILITY, PATENT
  • İstanbul Üniversitesi Adresli: Evet

Özet

Novel sulfonamidoindole-based hydrazones with a 2-(hydrazinocarbonyl)-3-phenyl-1H-indole-5-sulfonamide scaffold were synthesized and tested in enzyme inhibition assays against the tumor-associated carbonic anhydrase isoforms, hCA IX and XII, and the off-targets, hCA I and II. The compounds showed selectivity against hCA IX and XII over hCA I and II. Six compounds showed K-I values lower than 10 nM against hCA IX or XII. Molecular modeling studies were performed to suggest binding interactions between the ligand and the hCA active sites.