Selective trihydroxylated azepane inhibitors of NagZ, a glycosidase involved in Pseudomonas aeruginosa resistance to β-lactam antibiotics

J. Bouquet, D. T. King, G. Vadlamani, G. R. Benzie, B. Iorga, D. Ide, I. Adachi, A. Kato, D. J. Vocadlo, B. L. Mark, Y. Blériot, J. Désiré

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

The synthesis of a series of d-gluco-like configured 4,5,6-trihydroxyazepanes bearing a triazole, a sulfonamide or a fluorinated acetamide moiety at C-3 is described. These synthetic derivatives have been tested for their ability to selectively inhibit the muropeptide recycling glucosaminidase NagZ and to thereby increase sensitivity of Pseudomonas aeruginosa to β-lactams, a pathway with substantial therapeutic potential. While introduction of triazole and sulfamide groups failed to lead to glucosaminidase inhibitors, the NHCOCF3 analog proved to be a selective inhibitor of NagZ over other glucosaminidases including human O-GlcNAcase and lysosomal hexosaminidases HexA and B.

Original languageEnglish
Pages (from-to)4609-4619
Number of pages11
JournalOrganic and Biomolecular Chemistry
Volume15
Issue number21
DOIs
Publication statusPublished - 2017
Externally publishedYes

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