Sulfonamides linked to sulfonate esters via hydrazone functionality: synthesis, human carbonic anhydrase inhibitory activities, and molecular modeling studies

HAN M. İ., GÜNDÜZ M. G., Alçı G., Giovannuzzi S., YUVALI D., Supuran C. T., ...More

New Journal of Chemistry, vol.47, no.9, pp.4267-4276, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 47 Issue: 9
  • Publication Date: 2023
  • Doi Number: 10.1039/d2nj05703d
  • Journal Name: New Journal of Chemistry
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Biotechnology Research Abstracts, Chemical Abstracts Core, Chimica, Compendex, EMBASE, DIALNET
  • Page Numbers: pp.4267-4276
  • Hacettepe University Affiliated: Yes


© 2023 The Royal Society of Chemistry.In the present study, we synthesized novel carbonic anhydrase (CA, EC inhibitors by linking various sulfonate esters to a benzenesulfonamide fragment via hydrazone functionality (SH1-SH14). Following structural characterization using spectral techniques, the obtained molecules were screened for their inhibitory potential against tumor-associated human (h) isoforms hCA IX and XII, along with the physiologically dominant isoforms hCA I and II. Introducing methyl, methoxy or chlorine substituents into the para position of the terminal phenyl ring led to the most effective hCA IX and/or hCA XII inhibitors, with Ki values < 10 nM. Drug-likeness and pharmacokinetic profiles of the selected compounds were predicted using in silico techniques. Finally, molecular docking studies of the most effective inhibitor, 4-((2-(4-sulfamoylbenzoyl)hydrazono)methyl)phenyl 4-methoxybenzenesulfonate (SH3), against the tumor-associated hCA isoforms IX (Ki = 9.4 nM) and XII (Ki = 5.9 nM) were carried out to rationalize the inhibition data.