Selective trihydroxylated azepane inhibitors of NagZ, a glycosidase involved in Pseudomonas aeruginosa resistance to ß-lactam antibiotics.
Org Biomol Chem
; 15(21): 4609-4619, 2017 May 31.
Article
em En
| MEDLINE
| ID: mdl-28513749
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 ß-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.
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Base de dados:
MEDLINE
Assunto principal:
Pseudomonas aeruginosa
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Azepinas
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Beta-Lactamas
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Glicosídeo Hidrolases
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Antibacterianos
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article