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

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

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, vol.20, no.9, 2019 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 20 Issue: 9
  • Publication Date: 2019
  • Doi Number: 10.3390/ijms20092354
  • Journal Name: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Keywords: carbonic anhydrase, sulfonamides, hydrazones, enzyme inhibition, molecular modeling, MAMMALIAN ISOFORMS, DRUG DISCOVERY, DESIGN, SOLUBILITY, PATENT
  • Bezmialem Vakıf University Affiliated: Yes

Abstract

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.