A γ-Lactam Siderophore Antibiotic Effective against Multidrug-Resistant Gram-Negative Bacilli.
J Med Chem
; 63(11): 5990-6002, 2020 06 11.
Article
em En
| MEDLINE
| ID: mdl-32420736
ABSTRACT
Treatment of multidrug-resistant Gram-negative bacterial pathogens represents a critical clinical need. Here, we report a novel γ-lactam pyrazolidinone that targets penicillin-binding proteins (PBPs) and incorporates a siderophore moiety to facilitate uptake into the periplasm. The MIC values of γ-lactam YU253434, 1, are reported along with the finding that 1 is resistant to hydrolysis by all four classes of ß-lactamases. The druglike characteristics and mouse PK data are described along with the X-ray crystal structure of 1 binding to its target PBP3.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sideróforos
/
Farmacorresistência Bacteriana Múltipla
/
Lactamas
/
Antibacterianos
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article