Inhibition pattern of sulfamide-related compounds in binding to carbonic anhydrase isoforms I, II, VII, XII and XIV

Bioorg Med Chem. 2013 Mar 15;21(6):1410-8. doi: 10.1016/j.bmc.2012.10.048. Epub 2012 Nov 29.

Abstract

A set of sulfamides and sulfamates were synthesized and tested against several isoforms of carbonic anhydrase: CA I, CA II, CA VII, CA XII and CA XIV. The biological assays showed a broad range of inhibitory activity, and interesting results were found for several compounds in terms of activity (Ki <1μm) and selectivity: some aromatic sulfamides are active against CA I, CA II and/or CA VII; while they are less active in CA XII and CA XIV. On the other hand, bulky sulfamides are selective to CA VII. To understand the origin of the different inhibitory activity against each isozyme we used molecular modeling techniques such as docking and molecular dynamic simulations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Carbonic Anhydrase I / antagonists & inhibitors
  • Carbonic Anhydrase I / metabolism
  • Carbonic Anhydrase II / antagonists & inhibitors
  • Carbonic Anhydrase II / metabolism
  • Carbonic Anhydrase Inhibitors / chemical synthesis
  • Carbonic Anhydrase Inhibitors / chemistry*
  • Carbonic Anhydrase Inhibitors / metabolism
  • Carbonic Anhydrases / chemistry*
  • Carbonic Anhydrases / metabolism
  • Catalytic Domain
  • Humans
  • Molecular Docking Simulation
  • Protein Binding
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry*
  • Sulfonamides / metabolism

Substances

  • Carbonic Anhydrase Inhibitors
  • Sulfonamides
  • Carbonic Anhydrase I
  • Carbonic Anhydrase II
  • Carbonic Anhydrases
  • carbonic anhydrase VI
  • carbonic anhydrase XII
  • carbonic anhydrase XIV