Carbonic Anhydrase Inhibitors. Inhibition of Cytosolic Isoforms I, II, III, VII and XIII With Less Investigated Inorganic Anions

Bioorg Med Chem Lett. 2009 Apr 1;19(7):1855-7. doi: 10.1016/j.bmcl.2009.02.088. Epub 2009 Feb 26.

Abstract

An inhibition study of the cytosolic carbonic anhydrase (CA, EC 4.2.1.1) isoforms I, II, III, VII and XIII with anions such as stannate(IV), selenate(VI), tellurate(VI), perosmate(VIII), persulfate, pyrophosphate(V), pyrovanadate(V), tetraborate, persulfate, perrhenate(VII), perrutenate(VII), selenocyanate, iminodisulfonate, fluorosulfate and trithiocarbonate is reported. Trithiocarbonate was the best inhibitor detected, showing affinities of 8.7-9.9 microM for CA I-III, of 36.15 mM for CA VII and of 0.43 mM for CA XIII. Considering trithiocarbonate as lead, we show that compounds incorporating the new zinc-binding group CS2-, such as among other the dithiocarbamates, are even more active inhibitors, with submicromolar inhibitory activity. New classes of CA inhibitors are being detected based on the CS2- zinc-binding group.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anions / chemistry*
  • Carbonic Anhydrase I / chemistry
  • Carbonic Anhydrase I / metabolism
  • Carbonic Anhydrase II / chemistry
  • Carbonic Anhydrase II / metabolism
  • Carbonic Anhydrase III / chemistry
  • Carbonic Anhydrase III / metabolism
  • Carbonic Anhydrase Inhibitors / chemistry*
  • Carbonic Anhydrases / chemistry*
  • Carbonic Anhydrases / metabolism
  • Carrier Proteins / chemistry
  • Ethylenebis(dithiocarbamates) / chemistry
  • Humans
  • Protein Isoforms / chemistry
  • Protein Isoforms / metabolism
  • Thiones / chemistry
  • Zinc / chemistry

Substances

  • Anions
  • Carbonic Anhydrase Inhibitors
  • Carrier Proteins
  • Ethylenebis(dithiocarbamates)
  • Protein Isoforms
  • Thiones
  • zinc-binding protein
  • Carbonic Anhydrase I
  • Carbonic Anhydrase II
  • Carbonic Anhydrase III
  • CA13 protein, human
  • Carbonic Anhydrases
  • carbonic anhydrase VI
  • Zinc
  • trithiocarbonic acid