Abdoli Morteza, Angeli Andrea, Bozdag Murat, Carta Fabrizio, Kakanejadifard Ali, Saeidian Hamid, Supuran Claudiu T
a Department of Chemistry, Faculty of Science , Lorestan University , Khorramabad , Iran.
b Dipartimento di Chimica, Laboratorio di Chimica Bioinorganica , Università degli Studi di Firenze , Sesto Fiorentino, Florence , Italy.
J Enzyme Inhib Med Chem. 2017 Dec;32(1):1071-1078. doi: 10.1080/14756366.2017.1356295.
A series of benzo[d]thiazole-5- and 6-sulfonamides has been synthesized and investigated for the inhibition of several human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms, using ethoxzolamide (EZA) as lead molecule. 2-Amino-substituted, 2-acylamino- and halogenated (bromo-and iodo-derivatives at the heterocyclic ring) compounds led to several interesting inhibitors against the cytosolic hCA I, II and VII, as well as the transmembrane, tumor-associated hCA IX isoforms. Several subnanomolar/low nanomolar, isoform-selective sulfonamide inhibitors targeting hCA II, VII and IX were detected. The sharp structure-activity relationship for CA inhibition with this small series of derivatives, with important changes of activity observed even after minor changes in the scaffold or at the 2-amino moiety, make this class of scarcely investigated sulfonamides of particular interest for further investigations.
以乙氧唑胺（EZA）为先导分子，合成了一系列苯并[d]噻唑-5-和6-磺酰胺，并研究了它们对几种人（h）碳酸酐酶（CA，EC 4.2.1.1）同工型的抑制作用。2-氨基取代的、2-酰基氨基的以及卤代的（杂环上的溴代和碘代衍生物）化合物产生了几种针对胞质hCA I、II和VII以及跨膜、肿瘤相关hCA IX同工型的有趣抑制剂。检测到了几种针对hCA II、VII和IX的亚纳摩尔/低纳摩尔、同工型选择性磺酰胺抑制剂。这一小系列衍生物对CA抑制作用的结构-活性关系很明显，即使在支架或2-氨基部分有微小变化后也观察到活性的重要变化，使得这类研究较少的磺酰胺特别值得进一步研究。
