Synthesis and evaluation of 4-(1,3,4-oxadiazol-2-yl)-benzenesulfonamides as potent carbonic anhydrase inhibitors

Bioorg Med Chem Lett. 2020 Jan 15;30(2):126874. doi: 10.1016/j.bmcl.2019.126874. Epub 2019 Dec 4.

Abstract

Human Carbonic anhydrase (hCA) I and II are crucial targets for anti-acute mountain sickness. Twenty-one 4-(1,3,4-oxadiazol-2-yl) benzenesulfonamides were synthesized and screened against these two isoforms. The results illustrated that 5c, 5g, 5h, 5k were more potent against both hCA I and II than clinical drug AAZ. In particular, the value of compound 5c with hCA I (18.08 nM) was over 84-fold more than of AAZ with hCA I. The data of docking simulations were also in accord with the tendency of inhibitive activities. Furthermore, compound 6h, the methanesulfonate of 5h, showed better anti-hypoxia activity than AAZ in vivo, making it interesting lead compound.

Keywords: Anti-hypoxia; Benzenesulfonamide derivatives; Cytotoxicity; Docking simulations; hCA inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzenesulfonamides
  • Carbonic Anhydrase Inhibitors / pharmacology
  • Carbonic Anhydrase Inhibitors / therapeutic use*
  • Humans
  • Molecular Structure
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis*
  • Sulfonamides / chemistry

Substances

  • Carbonic Anhydrase Inhibitors
  • Sulfonamides