Cecchi Alessandro, Winum Jean-Yves, Innocenti Alessio, Vullo Daniela, Montero Jean-Louis, Scozzafava Andrea, Supuran Claudiu T
Università degli Studi di Firenze, Polo Scientifico, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, 50019 Sesto Fiorentino (Florence), Italy.
Bioorg Med Chem Lett. 2004 Dec 6;14(23):5775-80. doi: 10.1016/j.bmcl.2004.09.062.
A series of sulfonamides incorporating 4-thioureido-benzolamide moieties have been prepared from aminobenzolamide and thiophosgene followed by the reaction of the thiocyanato intermediate with aliphatic/aromatic amines or hydrazines. The new derivatives have been investigated as inhibitors of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), and more precisely of the cytosolic isozymes hCA I and II, as well as the tumor-associated isozyme hCA IX (all of human origin). The new compounds showed excellent inhibitory properties against all three isozymes with inhibition constants in the range of 0.6-62 nM against hCA I, 0.5-1.7 nM against hCA II and 3.2-23 nM against hCA IX, respectively. These derivatives are interesting candidates for the development of novel therapies targeting hypoxic tumors.
一系列含有4-硫脲基-苯甲酰胺部分的磺胺类化合物已由氨基苯甲酰胺和硫光气制备而成，随后硫氰酸酯中间体与脂肪族/芳香族胺或肼反应。这些新衍生物已作为锌酶碳酸酐酶（CA，EC 4.2.1.1）的抑制剂进行了研究，更确切地说是针对胞质同工酶hCA I和II以及肿瘤相关同工酶hCA IX（均源自人类）。这些新化合物对所有三种同工酶均表现出优异的抑制特性，对hCA I的抑制常数范围为0.6 - 62 nM，对hCA II为0.5 - 1.7 nM，对hCA IX为3.2 - 23 nM。这些衍生物是开发针对缺氧肿瘤的新型疗法的有趣候选物。
