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, vol.20, no.9, 2019 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 20 Issue: 9
  • Publication Date: 2019
  • Doi Number: 10.3390/ijms20092354
  • Title of Journal : INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

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.