Synthesis of novel dipeptide sulfonamide conjugates with effective carbonic anhydrase I, II, IX, and XII inhibitory properties

Bioorg Chem. 2018 Dec:81:311-318. doi: 10.1016/j.bioorg.2018.08.032. Epub 2018 Aug 27.

Abstract

Twenty-four novel sulfonamide derivatives incorporating dipeptide tails were synthesized by facile acylation reactions of homosulfanilamide through benzotriazole or dicyclohexyl carbodiimide (DCC) mediated coupling reactions. The carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity of the new compounds was assessed against four human (h) isoforms, hCA I, hCA II, hCA IX and hCA XII. Most of the synthesized compounds showed good in vitro carbonic anhydrase inhibitory properties, with inhibition constants in the low nanomolar range. Particularly, the new dipeptide-sulfonamide conjugates incorporating Ala, Phe and Met in the dipeptide sequence, showed the most effective inhibitory activity against to CA IX and XII.

Keywords: Carbonic anhydrase; Conjugate; Dipeptide; Homosulfanilamide; Inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm
  • Carbonic Anhydrase I / antagonists & inhibitors
  • Carbonic Anhydrase II / antagonists & inhibitors
  • Carbonic Anhydrase IX / antagonists & inhibitors
  • Carbonic Anhydrase Inhibitors / chemical synthesis
  • Carbonic Anhydrase Inhibitors / chemistry*
  • Dipeptides / chemical synthesis
  • Dipeptides / chemistry*
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry*

Substances

  • Antigens, Neoplasm
  • Carbonic Anhydrase Inhibitors
  • Dipeptides
  • Isoenzymes
  • Sulfonamides
  • Carbonic Anhydrase I
  • Carbonic Anhydrase II
  • CA2 protein, human
  • CA9 protein, human
  • Carbonic Anhydrase IX