New superacid synthesized (fluorinated) tertiary benzenesulfonamides acting as selective hCA IX inhibitors: toward a new mode of carbonic anhydrase inhibition by sulfonamides

Chem Commun (Camb). 2013 Jul 11;49(54):6015-7. doi: 10.1039/c3cc40858b.

Abstract

Tertiary substituted (fluorinated) benzenesulfonamides were synthesized in superacid HF/SbF5 and tested as inhibitors of human carbonic anhydrases (hCAs, EC 4.2.1.1). Strong selectivity toward tumor-associated hCA IX, without inhibiting the offtarget hCA II, was observed, pointing out to a new mechanism of action compared to classical sulfonamides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / chemistry*
  • Antigens, Neoplasm / metabolism
  • Carbonic Anhydrase II / antagonists & inhibitors
  • Carbonic Anhydrase II / metabolism
  • Carbonic Anhydrase IX
  • Carbonic Anhydrase Inhibitors / chemical synthesis*
  • Carbonic Anhydrase Inhibitors / chemistry
  • Carbonic Anhydrase Inhibitors / metabolism
  • Carbonic Anhydrases / chemistry*
  • Carbonic Anhydrases / metabolism
  • Humans
  • Protein Binding
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry*
  • Sulfonamides / metabolism

Substances

  • Antigens, Neoplasm
  • Carbonic Anhydrase Inhibitors
  • Sulfonamides
  • Carbonic Anhydrase II
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases