Ceruso Mariangela, Antel Sabrina, Scozzafava Andrea, Supuran Claudiu T
a Dipartimento di Chimica, Laboratorio di Chimica Bioinorganica , Università degli Studi di Firenze , Sesto Fiorentino (Firenze) , Italy and.
b Neurofarba Department , Università degli Studi di Firenze , Sesto Fiorentino (Florence) , Italy.
J Enzyme Inhib Med Chem. 2016;31(2):205-11. doi: 10.3109/14756366.2015.1014477. Epub 2015 Sep 4.
New ureido benzenesulfonamides incorporating a GABA moiety as a linker between the ureido and the sulfonamide functionalities were synthesized and their inhibition potency determined against both the predominant cytosolic (hCA I and II) and the transmembrane tumor-associated (hCA IX and XII) isoforms of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The majority of these compounds were medium potency inhibitors of the cytosolic isoform hCA I and effective hCA II inhibitors, whereas they showed strong inhibition of the two transmembrane tumor-associated isoforms hCA IX and XII, with KIs in nanomolar range. Only one derivative had a good selectivity for inhibition of the tumor-associated hCA IX target isoform over the cytosolic and physiologically dominant off-target hCA I and II, being thus a potential tool to develop new anticancer agents.
合成了新型脲基苯磺酰胺，其在脲基和磺酰胺官能团之间引入了γ-氨基丁酸（GABA）作为连接基团，并测定了它们对金属酶碳酸酐酶（CA，EC 4.2.1.1）的主要胞质同工型（hCA I和II）以及跨膜肿瘤相关同工型（hCA IX和XII）的抑制效力。这些化合物中的大多数是胞质同工型hCA I的中等效力抑制剂和有效的hCA II抑制剂，而它们对两种跨膜肿瘤相关同工型hCA IX和XII表现出强烈抑制作用，抑制常数（KI）在纳摩尔范围内。只有一种衍生物对肿瘤相关的hCA IX靶标同工型的抑制作用相对于胞质和生理上占主导的脱靶hCA I和II具有良好的选择性，因此是开发新型抗癌药物的潜在工具。
