CARBONIC ANHYDRASE INHIBITORS : 2-Substituted-1,3,4-Thiadiazole-5-Sulfamides act as powerful and selective inhibitors of the mitochondrial isozymes VA and VB over the cytosolic and membrane-associated carbonic anhydrases I, II AND IV

A series of 2-substitutes-1, 3,4-thiadiazole-5-sulfamides was prepared ans assayed as inhibitors of several carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the cytosolic CA I and II, the membrane-associated CA IV and the... [ view full abstract ]

A series of 2-substitutes-1, 3,4-thiadiazole-5-sulfamides was prepared ans assayed as inhibitors of several carbonic anhydrase (CA, EC 4.2.1.1) isoforms, the cytosolic CA I and II, the membrane-associated CA IV and the mitochondrial CA VA and VB. The new compounds showed weak inhibitory activitiy against hCA I (K1S of 102 nM- 7,42 µM), hCA II (K1S of 0,54-7,42 µM) and hCA IV (K1S of 4,32-10,05 µM) but were low nanomolar inhibitors of hCA VA and hCA VB, with inhibiton constants in the range of 4,2-32 nM and 1,3-74 nM, respectively. Furthermore, the selectivity ratios for inhibiting the mitochondrial enzymes over CAII were in the range of 67,5-415, making these sulfamides the first selective CA VA/VB inhibitors1.

1 Bioorganic and Medicinal Chemistry Letters 18 (2008) 6332-6335.