Ombouma Joanna, Vullo Daniela, Köhler Stephan, Dumy Pascal, Supuran Claudiu T, Winum Jean-Yves
a Institut des Biomolécules Max Mousseron (IBMM) UMR 5247 CNRS-ENSCM-UM1-UM2, Bâtiment de Recherche Max Mousseron, Ecole Nationale Supérieure de Chimie de Montpellier , Montpellier Cedex , France .
b Laboratorio di Chimica Bioinorganica , Polo Scientifico, Università degli Studi di Firenze , Sesto Fiorentino, Florence , Italy .
J Enzyme Inhib Med Chem. 2015 Dec;30(6):1010-2. doi: 10.3109/14756366.2014.986119. Epub 2015 Mar 20.
We investigated a series of N-hydroxysulfamides obtained by Ferrier sulfamidoglycosylation for the inhibition of two bacterial carbonic anhydrases (CAs, EC 4.2.1.1) present in the pathogen Brucella suis. bsCA I was moderately inhibited by these compounds with inhibition constants ranging between 522 and 958 nM and no notable differences of activity between the acetylated or the corresponding deacetylated derivatives. The compounds incorporating two trans-acetates and the corresponding deprotected ones were the most effective inhibitors in the series. bsCA II was better inhibited, with inhibition constants ranging between 59.8 and 799 nM. The acetylated derivatives were generally better bsCA II inhibitors compared to the corresponding deacetylated compounds. Although these compounds were not highly isoform-selective CA inhibitors (CAIs) for the bacterial over the human CA isoforms, some of them possess inhibition profiles that make them interesting leads for obtaining better and more isoform-selective CAIs targeting bacterial enzymes.
我们研究了一系列通过费里尔磺酰胺糖基化反应得到的N-羟基磺酰胺，以考察其对猪布鲁氏菌中存在的两种细菌碳酸酐酶（CAs，EC 4.2.1.1）的抑制作用。这些化合物对bsCA I有中等程度的抑制作用，抑制常数在522至958 nM之间，乙酰化衍生物或相应的脱乙酰化衍生物之间的活性没有显著差异。该系列中，含有两个反式乙酸酯的化合物及其相应的脱保护化合物是最有效的抑制剂。bsCA II受到的抑制作用更强，抑制常数在59.8至799 nM之间。与相应的脱乙酰化化合物相比，乙酰化衍生物通常是更好的bsCA II抑制剂。尽管这些化合物并非对细菌CA同工型具有高度亚型选择性的碳酸酐酶抑制剂（CAIs），但其中一些化合物的抑制特性使其成为获得更好、更具亚型选择性的靶向细菌酶的CAIs的有趣先导化合物。
