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)-β-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 (KIs of 9.4 −13.3 μM), were efficient hCA II inhibitors (KIs 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 (KI of 10 nM). These derivatives also showed excellent hCA VII inhibitory activity (KIs of 10–79 nM), being less efficient as inhibitors of the transmembrane isoforms hCA IX (KIs of 10–4500 nM) and hCA XIV (KIs 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.