N-glycosyl-N-hydroxysulfamides as potent inhibitors of Brucella suis carbonic anhydrases

Joanna Ombouma (1) , Daniela Vullo (2) , Stephan Köhler (3) , Pascal Dumy (4, 1) , Claudiu T. Supuran (2) , Jean-Yves Winum (1)

1 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]
2 LCBI-UniFI - Laboratorio di Chimica Bioinorganica [UniFI, Firenze] = Laboratory of Bioinorganic Chemistry [UniFI Florence]
3 IRIM - Institut de Recherche en Infectiologie de Montpellier
4 LEDSS - Laboratoire d'études dynamiques et structurales de la sélectivité

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.

Mots clés: Brucella suis; N-hydroxysulfamide; carbonic anhydrase; glycoinhibitor; glycosyl derivative

Domaines: Chimie; Chimie organique

Joanna Ombouma, Daniela Vullo, Stephan Köhler, Pascal Dumy, Claudiu T. Supuran, et al.. N-glycosyl-N-hydroxysulfamides as potent inhibitors of Brucella suis carbonic anhydrases. Journal of Enzyme Inhibition and Medicinal Chemistry, 2014, 30 (6), pp.1010-1012. ⟨10.3109/14756366.2014.986119⟩. ⟨hal-02425102⟩