title: N-glycosyl-N-hydroxysulfamides as potent inhibitors of Brucella suis carbonic anhydrases.
abstract: 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.
authors: 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 .
authors: Joanna
authors: J
authors: Ombouma
authors: b Laboratorio di Chimica Bioinorganica , Polo Scientifico, Università degli Studi di Firenze , Sesto Fiorentino, Florence , Italy .
authors: Daniela
authors: D
authors: Vullo
authors: c Centre d'Études d'Agents Pathogènes et Biotechnologies pour la Santé (CPBS), UMR5236, CNRS-Université Montpellier I-Université Montpellier II , Montpellier Cedex , France , and.
authors: Stephan
authors: S
authors: Köhler
authors: 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 .
authors: Pascal
authors: P
authors: Dumy
authors: d Neurofarba Department , Section of Pharmaceutical and Nutriceutical Sciences, Università degli Studi di Firenze , Via Ugo Schiff, Florence , Italy.
authors: Claudiu T
authors: CT
authors: Supuran
authors: 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 .
authors: Jean-Yves
authors: JY
authors: Winum
mesh_terms: D000617:Aminoglycosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D041021:Brucella suis / Q000201:enzymology*; D024401:Carbonic Anhydrase I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000617:Aminoglycosides; D002257:Carbonic Anhydrase Inhibitors; D013449:Sulfonamides; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II
keywords: Brucella suis; N-hydroxysulfamide; carbonic anhydrase; glycoinhibitor; glycosyl derivative