Sezione di Scienze Farmaceutiche e Nutraceutiche, Neurofarba Dept., Università degli Studi di Firenze, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.
Faculty of Medicine and Health Technology, Tampere University, 33100 Tampere, Finland.
Int J Mol Sci. 2018 Dec 8;19(12):3946. doi: 10.3390/ijms19123946.
A newly described β-carbonic anhydrase (CA, EC 4.2.1.1) from the pathogenic protozoan , EhiCA, was recently shown to possess a significant catalytic activity for the physiologic CO₂ hydration reaction (k of 6.7 × 10⁵ s and a k/K of 8.9 × 10⁷ M s). A panel of sulphonamides and one sulfamate, some of which are clinically used drugs, were investigated for their inhibitory properties against EhiCA. The best inhibitors detected in the study were 4-hydroxymethyl/ethyl-benzenesulfonamide (Ks of 36⁻89 nM), whereas some sulfanilyl-sulfonamides showed activities in the range of 285⁻331 nM. Acetazolamide, methazolamide, ethoxzolamide, and dichlorophenamide were less effective inhibitors (Ks of 509⁻845 nM) compared to other sulfonamides investigated here. As β-CAs are not present in vertebrates, the present study may be useful for detecting lead compounds for the design of more effective inhibitors with potential to develop anti-infectives with alternative mechanisms of action.
最近，从致病性原生动物 中描述了一种新型的β-碳酸酐酶（CA，EC 4.2.1.1），该酶对生理 CO₂水合反应具有显著的催化活性（k 值为 6.7×10⁵ s，k/K 值为 8.9×10⁷ M s）。研究了一组磺胺类药物和一种磺胺酸盐对 EhiCA 的抑制特性，其中一些是临床使用的药物。在研究中检测到的最佳抑制剂是 4-羟甲基/乙基-苯磺酰胺（Ks 为 36⁻89 nM），而一些磺胺基磺酰胺的活性范围为 285⁻331 nM。与这里研究的其他磺胺类药物相比，乙酰唑胺、甲唑胺、依索唑胺和双氯苯酰胺的抑制作用较弱（Ks 为 509⁻845 nM）。由于β-CAs 不存在于脊椎动物中，因此本研究可能有助于检测先导化合物，以设计更有效的抑制剂，这些抑制剂具有开发具有替代作用机制的抗感染药物的潜力。
