Carbonic anhydrase inhibitors. Inhibition of transmembrane isoforms IX, XII, and XIV with less investigated anions including trithiocarbonate and dithiocarbamate

An inhibition study of the transmembrane carbonic anhydrase (CA, EC 4.2.1.1) isoforms IX, XII (tumor-associated), and XIV 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. Selenate, perosmate, and pyrophosphate were ineffective inhibitors, whereas most of these anions inhibited the three enzymes in the millimolar-submillimolar range. Trithiocarbonate and diethyldithiocarbamate were the best CA IX inhibitors (K(I)s of 1.4-9.7 mu M), but trithiocarbonate showed less affinity for CA XII and XIV (K(I)s of 0.12-0.66 mM). N,N-Diethyldithiocarbamate was a low micromolar inhibitor also against CA XII and XIV (KIs of 1.0-1.1 mu M), suggesting that this new zinc-binding group (CS2-) may lead to efficient inhibitors targeting transmembrane CAs. (C) 2010 Elsevier Ltd. All rights reserved.