Carbonic anhydrase inhibitors : 2-substituted-1,3,4-thiadiazole-5sulfamides act as powerful and selective inhibitors of the microchondrial isozymes VA and VB over the cytosolic and membrane-associated carbonic anhydrase I, II and IV. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Bioorganic and Medicinal Chemistry Letters Année : 2008

Carbonic anhydrase inhibitors : 2-substituted-1,3,4-thiadiazole-5sulfamides act as powerful and selective inhibitors of the microchondrial isozymes VA and VB over the cytosolic and membrane-associated carbonic anhydrase I, II and IV.

Résumé

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 (K(I)s of 102 nM-7.42 microM), hCA II (K(I)s of 0.54-7.42 microM) and hCA IV (K(I)s of 4.32-10.05 microM) 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.

Dates et versions

hal-00355804 , version 1 (24-01-2009)

Identifiants

Citer

Fatma-Zohra Smaine, F. Pacchiano, Marouan Rami, Véronique Barragan-Montero, Daniela Vullo, et al.. Carbonic anhydrase inhibitors : 2-substituted-1,3,4-thiadiazole-5sulfamides act as powerful and selective inhibitors of the microchondrial isozymes VA and VB over the cytosolic and membrane-associated carbonic anhydrase I, II and IV.. Bioorganic and Medicinal Chemistry Letters, 2008, 18, pp.6332-6335. ⟨10.1016/j.bmcl.2008.10.093⟩. ⟨hal-00355804⟩
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