Synthesis and carbonic anhydrase inhibitory properties of novel 4-(2-aminoethyl)benzenesulfonamide-dipeptide conjugates

Bioorg Chem. 2019 Mar:83:414-423. doi: 10.1016/j.bioorg.2018.11.003. Epub 2018 Nov 3.

Abstract

Thirty novel sulfonamide derivatives incorporating dipeptide were synthesized by facile acylation through benzotriazole mediated reactions and their structures were identified by 1H NMR, 13C NMR, MS and FT-IR spectroscopic techniques and elemental analysis. 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 IV and hCA XII. Most of the synthesized compounds showed excellent in vitro carbonic anhydrase inhibitory properties comparable to those of the clinically used drug acetazolamide (AAZ). The new unprotected dipeptide-sulfonamide conjugates showed very effective inhibitory activity, in the low nanomolar range against II and XII, being less effective as hCA I and IV inhibitors. Four of the thirty compounds also showed strong inhibitory activity against hCA XII compared to AAZ.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbonic Anhydrase Inhibitors / chemical synthesis
  • Carbonic Anhydrase Inhibitors / chemistry*
  • Carbonic Anhydrases / chemistry
  • Dipeptides / chemical synthesis
  • Dipeptides / chemistry*
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Molecular Structure
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry*

Substances

  • Carbonic Anhydrase Inhibitors
  • Dipeptides
  • Isoenzymes
  • Sulfonamides
  • Carbonic Anhydrases