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

Int J Mol Sci. 2019 May 12;20(9):2354. doi: 10.3390/ijms20092354.


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 KI 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.

Keywords: carbonic anhydrase; enzyme inhibition; hydrazones; molecular modeling; sulfonamides.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Binding Sites
  • Carbonic Anhydrase IX / antagonists & inhibitors*
  • Carbonic Anhydrase IX / chemistry
  • Carbonic Anhydrase IX / metabolism
  • Carbonic Anhydrase Inhibitors / chemical synthesis*
  • Carbonic Anhydrase Inhibitors / pharmacology
  • Humans
  • Hydrazones / chemistry
  • Indoles / chemistry
  • Molecular Docking Simulation
  • Protein Binding
  • Sulfonamides / chemistry


  • Antineoplastic Agents
  • Carbonic Anhydrase Inhibitors
  • Hydrazones
  • Indoles
  • Sulfonamides
  • Carbonic Anhydrase IX