Carbonic anhydrase inhibitors. Inhibition of cytosolic isoforms I, II, III, VII and XIII with less investigated inorganic anions

Alessio Innocenti, Andrea Scozzafava, Claudiu T. Supuran, Alessio Innocenti, Andrea Scozzafava, Claudiu T. Supuran

Index: Bioorg. Med. Chem. Lett. 19 , 1855-7, (2009)

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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.