Investigation of carbonic anhydrase inhibitory potency of (Z/E)-alkyl N'-benzyl- N-(arylsulfonyl)-carbamimidothioates

Future Med Chem. 2023 Apr;15(7):615-627. doi: 10.4155/fmc-2022-0287. Epub 2023 May 4.

Abstract

Aim: Among 15 human (h) carbonic anhydrase (CA; EC 4.2.1.1) isoforms, two (hCA IX and XII) play important roles in the growth and survival of tumor cells, making them therapeutic targets for cancer treatment. This study aimed to develop novel sulfonamide-based compounds as selective hCA IX and XII inhibitors. Materials & methods: A library of novel N-sulfonyl carbamimidothioates was obtained for CA inhibitory activity studies against four hCA isoforms. Results: None of the developed compounds displayed inhibitory potential against off-target isoforms hCA I and II. However, they effectively inhibited tumor-associated hCA IX and XII. Conclusion: The present study suggests potent lead compounds as selective hCA IX and XII inhibitors with anticancer activity.

Keywords: (Z/E)-alkyl N'-benzyl-N-(arylsulfonyl)-carbamimidothioates; antitumor; carbonic anhydrase; inhibitors; sulfonamides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm
  • Carbonic Anhydrase IX
  • Carbonic Anhydrase Inhibitors / pharmacology
  • Carbonic Anhydrases* / metabolism
  • Humans
  • Molecular Structure
  • Neoplasms*
  • Structure-Activity Relationship

Substances

  • Carbonic Anhydrases
  • Carbonic Anhydrase IX
  • Carbonic Anhydrase Inhibitors
  • Antigens, Neoplasm