Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Neurofarba Department, Sezione di Chimica Farmaceutica e Nutraceutica, Università degli Studi di Firenze, Firenze, Italy.
J Enzyme Inhib Med Chem. 2021 Dec;36(1):329-334. doi: 10.1080/14756366.2020.1863958.
Sulphonamides and their isosteres are classical inhibitors of the carbonic anhydrase (CAs, EC 4.2.1.1) metalloenzymes. The protozoan pathogen encodes two such enzymes belonging to the β-class, TvaCA1 and TvaCA2. Here we report the first sulphonamide inhibition study of TvaCA1, with a series of simple aromatic/heterocyclic primary sulphonamides as well as with clinically approved/investigational drugs for a range of pathologies (diuretics, antiglaucoma, antiepileptic, antiobesity, and antitumor drugs). TvaCA1 was effectively inhibited by acetazolamide and ethoxzolamide, with Ks of 391 and 283 nM, respectively, whereas many other simple or clinically used sulphonamides were micromolar inhibitors or did not efficiently inhibit the enzyme. Finding more effective TvaCA1 inhibitors may constitute an innovative approach for fighting trichomoniasis, a sexually transmitted infection, caused by .
磺胺类药物及其同系物是碳酸酐酶（CA，EC 4.2.1.1）金属酶的经典抑制剂。原生动物病原体 编码两种属于β类的此类酶，TvaCA1 和 TvaCA2。在这里，我们报告了对 TvaCA1 的第一个磺胺类抑制研究，使用了一系列简单的芳香族/杂环初级磺胺类药物以及一系列用于治疗各种病理的临床批准/研究药物（利尿剂、降眼压药、抗癫痫药、减肥药和抗肿瘤药）。TvaCA1 被乙酰唑胺和乙氧唑胺有效抑制，Ks 值分别为 391 和 283 nM，而许多其他简单或临床使用的磺胺类药物是微摩尔抑制剂或不能有效抑制该酶。寻找更有效的 TvaCA1 抑制剂可能是对抗滴虫病的一种创新方法，滴虫病是一种由 引起的性传播感染。
