Saccharin sulfonamides as inhibitors of carbonic anhydrases I, II, VII, XII, and XIII

Biomed Res Int. 2014;2014:638902. doi: 10.1155/2014/638902. Epub 2014 Sep 3.

Abstract

A series of modified saccharin sulfonamides have been designed as carbonic anhydrase (CA) inhibitors and synthesized. Their binding to CA isoforms I, II, VII, XII, and XIII was measured by the fluorescent thermal shift assay (FTSA) and isothermal titration calorimetry (ITC). Saccharin bound the CAs weakly, exhibiting the affinities of 1-10 mM for four CAs except CA I where binding could not be detected. Several sulfonamide-bearing saccharines exhibited strong affinities of 1-10 nM towards particular CA isoforms. The functional group binding Gibbs free energy additivity maps are presented which may provide insights into the design of compounds with increased affinity towards selected CAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calorimetry
  • Carbonic Anhydrase Inhibitors / chemistry
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Carbonic Anhydrases / metabolism*
  • Fluorescence
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism
  • Molecular Docking Simulation
  • Recombinant Proteins / metabolism
  • Saccharin / chemistry
  • Saccharin / pharmacology*
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*
  • Thermodynamics

Substances

  • Carbonic Anhydrase Inhibitors
  • Isoenzymes
  • Recombinant Proteins
  • Sulfonamides
  • Carbonic Anhydrases
  • Saccharin