Novel Sulfamide-Containing Compounds as Selective Carbonic Anhydrase I Inhibitors

Molecules. 2017 Jun 24;22(7):1049. doi: 10.3390/molecules22071049.

Abstract

The development of isoform selective inhibitors of the carbonic anhydrase (CA; EC 4.2.1.1) enzymes represents the key approach for the successful development of druggable small molecules. Herein we report a series of new benzenesulfamide derivatives (-NH-SO₂NH₂) bearing the 1-benzhydrylpiperazine tail and connected by means of a β-alanyl or nipecotyl spacer. All compounds 6a-l were investigated in vitro for their ability to inhibit the physiological relevant human (h) CA isoforms such as I, II, IV and IX. Molecular modeling provided further structural support to enzyme inhibition data and structure-activity relationship. In conclusion the hCA I resulted the most inhibited isoform, whereas all the remaining ones showed different inhibition profiles.

Keywords: carbonic anhydrase inhibitors (CAIs); structure-activity-relationship (SAR); sulfamides.

MeSH terms

  • Benzene Derivatives / chemical synthesis*
  • Benzene Derivatives / chemistry
  • Benzene Derivatives / pharmacology
  • Carbonic Anhydrase I / antagonists & inhibitors
  • Carbonic Anhydrase Inhibitors / chemical synthesis*
  • Carbonic Anhydrase Inhibitors / chemistry
  • Carbonic Anhydrase Inhibitors / pharmacology
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis*
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology

Substances

  • Benzene Derivatives
  • Carbonic Anhydrase Inhibitors
  • Small Molecule Libraries
  • Sulfonamides
  • Carbonic Anhydrase I