Carbonic anhydrase inhibitors. Inhibition of isoforms I, II, IV, VA, VII, IX, and XIV with sulfonamides incorporating fructopyranose-thioureido tails

A series of aromatic/heterocyclic sulfonamides incorporating 2,3:4,5-bis-O-(isopropylidene)-beta-D-fructopyranosyl-thioureido moieties has been synthesized and assayed for the inhibition of seven human isoforms of the zinc enzyme carbonic anhydrase (hCA, EC 4.2.1.1). The new derivatives behaved as weak hCA I inhibitors (K(I)s of 9.4 -13.3 mu M), were efficient hCA II inhibitors (K(I)s of 6-750 nM), and slightly inhibited isoforms hCA IV and hCA VA. Only the sulfanilamide derivative showed efficient and selective inhibition of hCA IV (K-I of 10 nM). These derivatives also showed excellent hCA VII inhibitory activity (K(I)s of 1079 nM), being less efficient as inhibitors of the transmembrane isoforms hCA IX (K(I)s of 10-4500 nM) and hCA XIV (K(I)s of 21-3500 nM). Two of the new compounds showed anticonvulsant action in a maximal electroshock seizure test in mice, with the fluorosulfanilamide derivative being a more efficient anticonvulsant than the antiepileptic drug topiramate. (c) 2007 Elsevier Ltd. All rights reserved.