30457-35-3Relevant articles and documents
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
Smaine, Fatma-Zohra,Pacchiano, Fabio,Rami, Marouan,Barragan-Montero, Veronique,Vullo, Daniela,Scozzafava, Andrea,Winum, Jean-Yves,Supuran, Claudiu T.
experimental part, p. 6332 - 6335 (2009/09/06)
A series of 2-substituted-1,3,4-thiadiazole-5-sulfamides was prepared and 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 activity against hCA I (KIs of 102 nM-7.42 μM), hCA II (KIs of 0.54-7.42 μM) and hCA IV (KIs of 4.32-10.05 μM) but were low nanomolar inhibitors of hCA VA and hCA VB, with inhibition 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 CA II were in the range of 67.5-415, making these sulfamides the first selective CA VA/VB inhibitors.