Smaine Fatma-Zohra, Pacchiano Fabio, Rami Marouan, Barragan-Montero Véronique, Vullo Daniela, Scozzafava Andrea, Winum Jean-Yves, Supuran Claudiu T
Institut des Biomolécules Max Mousseron UMR 5247 CNRS-UM1-UM2 Bâtiment de Recherche Max Mousseron, Ecole Nationale Supérieure de Chimie de Montpellier, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex, France.
Bioorg Med Chem Lett. 2008 Dec 15;18(24):6332-5. doi: 10.1016/j.bmcl.2008.10.093. Epub 2008 Nov 1.
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.
制备了一系列2-取代-1,3,4-噻二唑-5-磺酰胺，并作为几种碳酸酐酶（CA，EC 4.2.1.1）同工型的抑制剂进行了测定，这些同工型包括胞质CA I和II、膜相关CA IV以及线粒体CA VA和VB。新化合物对hCA I（抑制常数K(I)为102 nM - 7.42 μM）、hCA II（K(I)为0.54 - 7.42 μM）和hCA IV（K(I)为4.32 - 10.05 μM）显示出较弱的抑制活性，但对hCA VA和hCA VB是低纳摩尔级抑制剂，抑制常数分别在4.2 - 32 nM和1.3 - 74 nM范围内。此外，抑制线粒体酶相对于CA II的选择性比率在67.5 - 415范围内，使得这些磺酰胺成为首批选择性CA VA/VB抑制剂。
