Aurones and derivatives as promising New Delhi metallo-ß-lactamase (NDM-1) inhibitors.
Bioorg Med Chem
; 97: 117559, 2024 01 01.
Article
em En
| MEDLINE
| ID: mdl-38109811
ABSTRACT
Bacterial resistance is undoubtedly one of the main public health concerns especially with the emergence of metallo-ß-lactamases (MBLs) able to hydrolytically inactivate ß-lactam antibiotics. Currently, there are no inhibitors of MBLs in clinical use to rescue antibiotic action and the New Delhi metallo-ß-lactamase-1 (NDM-1) is still considered as one of the most relevant targets for inhibitor development. Following a fragment-based strategy to find new NDM-1 inhibitors, we identified aurone as a promising scaffold. A series of 60 derivatives were then evaluated and two of them were identified as promising inhibitors with Ki values as low as 1.7 and 2.5 µM. Moreover, these two most active compounds were able to potentiate meropenem in in vitro antimicrobial susceptibility assays. The molecular modelling provided insights about their likely interactions with the active site of NDM-1, thus enabling further improvement in the structure of this new inhibitor family.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Benzofuranos
/
Beta-Lactamases
/
Inibidores de beta-Lactamases
Idioma:
En
Revista:
Bioorg Med Chem
/
Bioorg. med. chem
/
Bioorganic & medicinal chemistry
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
França