Optimization of novel monobactams with activity against carbapenem-resistant Enterobacteriaceae - Identification of LYS228.
Bioorg Med Chem Lett
; 28(4): 748-755, 2018 02 15.
Article
em En
| MEDLINE
| ID: mdl-29336873
ABSTRACT
Metallo-ß-lactamases (MBLs), such as New Delhi metallo-ß-lactamase (NDM-1) have spread world-wide and present a serious threat. Expression of MBLs confers resistance in Gram-negative bacteria to all classes of ß-lactam antibiotics, with the exception of monobactams, which are intrinsically stable to MBLs. However, existing first generation monobactam drugs like aztreonam have limited clinical utility against MBL-expressing strains because they are impacted by serine ß-lactamases (SBLs), which are often co-expressed in clinical isolates. Here, we optimized novel monobactams for stability against SBLs, which led to the identification of LYS228 (compound 31). LYS228 is potent in the presence of all classes of ß-lactamases and shows potent activity against carbapenem-resistant isolates of Enterobacteriaceae (CRE).
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
3_ND
Base de dados:
MEDLINE
Assunto principal:
Proteínas de Bactérias
/
Beta-Lactamases
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Monobactamas
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Resistência beta-Lactâmica
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Enterobacteriáceas Resistentes a Carbapenêmicos
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Antibacterianos
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Ano de publicação:
2018
Tipo de documento:
Article