Inhibition of human carbonic anhydrase isoforms I-XIV with sulfonamides incorporating fluorine and 1,3,5-triazine moieties

Bioorg Med Chem. 2013 Nov 15;21(22):6929-36. doi: 10.1016/j.bmc.2013.09.031. Epub 2013 Sep 19.

Abstract

Reaction of cyanuryl fluoride with sulfanilamide or 4-aminoethylbenzenesulfonamide afforded triazinyl-substituted benzenesulfonamides incorporating fluorine, which were further derivatized by reaction with amines, amino alcohols, amino acids or amino acid esters. Inhibition studies of all the human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms, hCA I-XIV with these compounds revealed that they show moderate-weak inhibition of hCA III, IV, VA and XIII, rather moderate inhibition against hCA I, VI, and IX, and excellent inhibition of the physiologically relevant hCA II, VII and XII. The inhibition profile of these fluorine containing triazinyl sulfonamides is thus very different from the corresponding analogs incorporating chlorine, which were previously investigated as inhibitors of some of these enzymes.

Keywords: 1,3,5-Triazine; Carbonic anhydrase; Isoform-selective inhibitor; Sulfonamide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbonic Anhydrase I / chemistry*
  • Carbonic Anhydrase I / metabolism*
  • Carbonic Anhydrase Inhibitors / chemical synthesis
  • Carbonic Anhydrase Inhibitors / chemistry*
  • Carbonic Anhydrase Inhibitors / pharmacology
  • Enzyme Activation / drug effects
  • Fluorine / chemistry*
  • Humans
  • Isoenzymes / chemistry
  • Isoenzymes / metabolism
  • Protein Binding / drug effects
  • Structure-Activity Relationship
  • Sulfanilamide
  • Sulfanilamides / chemical synthesis
  • Sulfanilamides / chemistry*
  • Sulfanilamides / pharmacology
  • Triazines / chemistry*

Substances

  • Carbonic Anhydrase Inhibitors
  • Isoenzymes
  • Sulfanilamides
  • Triazines
  • Sulfanilamide
  • Fluorine
  • Carbonic Anhydrase I