X-ray crystallography-promoted drug design of carbonic anhydrase inhibitors

Chem Commun (Camb). 2015 Apr 28;51(33):7108-11. doi: 10.1039/c5cc01854d.

Abstract

1-N-Alkylated-6-sulfamoyl saccharin derivatives were prepared and assayed as carbonic anhydrase inhibitors (CAIs). During X-ray crystallographic experiments an unexpected hydrolysis of the isothiazole ring was evidenced which allowed us to prepare highly potent enzyme inhibitors with selectivity for some isoforms with medical applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Carbonic Anhydrases / chemistry*
  • Carbonic Anhydrases / metabolism*
  • Crystallography, X-Ray
  • Drug Design*
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / chemistry
  • Models, Molecular
  • Protein Conformation

Substances

  • Carbonic Anhydrase Inhibitors
  • Isoenzymes
  • Carbonic Anhydrases