Vullo Daniela, Kumar R Siva Sai, Scozzafava Andrea, Ferry James G, Supuran Claudiu T
a Chemistry Department, Laboratorio di Chimica Bioinorganica , Università degli Studi di Firenze , Florence , Italy.
b Department of Biochemistry and Molecular Biology, Eberly College of Science , The Pennsylvania State University , University Park , PA , USA.
J Enzyme Inhib Med Chem. 2018 Dec;33(1):31-36. doi: 10.1080/14756366.2017.1388233.
The β-carbonic anhydrases (CAs, EC 4.2.1.1) from the pathogenic bacterium Clostridium perfringens (CpeCA) was recently characterised kinetically and for its anion inhibition profile. In the search of effective CpeCA inhibitors, possibly useful to inhibit the growth/pathogenicity of this bacterium, we report here an inhibition study of this enzyme with a panel of aromatic, heterocyclic and sugar sulphonamides/sulphamates. Some sulphonamides, such as acetazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, sulthiame and 4-(2-hydroxymethyl-4-nitrophenyl-sulphonamido)ethylbenzenesulphonamide were effective CpeCA inhibitors, with Ks in the range of 37.4-71.6 nM. Zonisamide and saccharin were the least effective such inhibitors, whereas many other aromatic and heterocyclic sulphonamides were moderate - weak inhibitors with Ks ranging between 113 and 8755 nM. Thus, this study provides the basis for developing better clostridial enzyme inhibitors with potential as antiinfectives with a new mechanism of action.
来自致病性细菌产气荚膜梭菌的β-碳酸酐酶（CAs，EC 4.2.1.1，即CpeCA）最近在动力学及其阴离子抑制特性方面得到了表征。在寻找可能有助于抑制该细菌生长/致病性的有效CpeCA抑制剂的过程中，我们在此报告了用一组芳香族、杂环和糖类磺酰胺/氨基磺酸盐对该酶进行的抑制研究。一些磺酰胺，如乙酰唑胺、乙氧唑胺、二氯苯酰胺、多佐胺、舒噻美和4-（2-羟甲基-4-硝基苯基-磺酰胺基）乙基苯磺酰胺是有效的CpeCA抑制剂，其Ks值在37.4 - 71.6 nM范围内。唑尼沙胺和糖精是效果最差的此类抑制剂，而许多其他芳香族和杂环磺酰胺是中度 - 弱抑制剂，Ks值在113至8755 nM之间。因此，本研究为开发具有潜在抗感染作用且作用机制新颖的更好的梭菌酶抑制剂提供了基础。
