Nonaromatic sulfonamide group as an ideal anchor for potent human carbonic anhydrase inhibitors: role of hydrogen-bonding networks in ligand binding and drug design

J Med Chem. 2002 Aug 15;45(17):3583-7. doi: 10.1021/jm011131t.

Abstract

X-ray crystal structures of the adducts of human carbonic anhydrase (hCA) isozyme II with derivatives incorporating a sulfamide or sulfamic acid moiety are reported. The absence of a C-SO(2)NH(2) bond in the first type of compound can be exploited for the design of more potent and selective CA inhibitors. This study also explains why sulfate is a several-orders-of-magnitude weaker CA inhibitor compared to derivatives incorporating sulfonamide/sulfamide moieties.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbonic Anhydrase II / chemistry*
  • Carbonic Anhydrase Inhibitors / chemistry*
  • Crystallography, X-Ray
  • Drug Design
  • Humans
  • Hydrogen Bonding
  • Isoenzymes / chemistry
  • Ligands
  • Models, Molecular
  • Structure-Activity Relationship
  • Sulfonamides / chemistry*
  • Sulfonic Acids / chemistry

Substances

  • Carbonic Anhydrase Inhibitors
  • Isoenzymes
  • Ligands
  • Sulfonamides
  • Sulfonic Acids
  • sulfamic acid
  • Carbonic Anhydrase II