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Issue 21, 2017
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Selective trihydroxylated azepane inhibitors of NagZ, a glycosidase involved in Pseudomonas aeruginosa resistance to β-lactam antibiotics

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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.

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

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Publication details

The article was received on 04 Apr 2017, accepted on 09 May 2017 and first published on 09 May 2017


Article type: Paper
DOI: 10.1039/C7OB00838D
Citation: Org. Biomol. Chem., 2017,15, 4609-4619
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    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 and J. Désiré, Org. Biomol. Chem., 2017, 15, 4609
    DOI: 10.1039/C7OB00838D

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