Tellurides Bearing Sulfonamides as Novel Inhibitors of Leishmanial Carbonic Anhydrase with Potent Antileishmanial Activity

We report for the first time a novel
series of tellurides bearing
sulfonamide as selective and potent inhibitors of the β-class
carbonic anhydrase (CA; EC 4.2.1.1) enzyme expressed in Leishmania donovani protozoa. Such derivatives showed
high activity against axenic amastigotes, and among them, compound 5g (4-(((3,4,5-trimethoxyphenyl)­tellanyl)­methyl)­benzenesulfonamide)
showed an IC50 of 0.02 μM being highly selective
for the parasites over THP-1 cells with a selectivity index of 300.
The in vitro and in vivo toxicity experiments showed compound 5g to possess a safe profile and thus paving the way for tellurium-containing
compounds as novel drug entities.

本研究首次报道了一类以磺酰胺（sulfonamide）为官能团的新型碲化物系列，其可作为杜氏利什曼原虫（Leishmania donovani）原生动物表达的β类碳酸酐酶（carbonic anhydrase, CA; EC 4.2.1.1）的强效选择性抑制剂。此类衍生物对无菌培养的无鞭毛体展现出优异抑制活性，其中化合物5g（4-(((3,4,5-三甲氧基苯基)碲基)甲基)苯磺酰胺）的半最大抑制浓度（IC50）为0.02 μM，且相较于THP-1细胞对该寄生虫具有极高选择性，选择性指数高达300。体外与体内毒性实验结果表明，化合物5g具备良好的安全特性，从而为含碲化合物作为新型药物实体的研发铺平了道路。