A novel tricyclic ß-lactam exhibiting potent antibacterial activities against carbapenem-resistant Enterobacterales: Synthesis and structure-activity-relationships.
Bioorg Med Chem
; 46: 116343, 2021 09 15.
Article
em En
| MEDLINE
| ID: mdl-34450571
ABSTRACT
A series of tricyclic ß-lactams were synthesized and evaluated for in vitro antibacterial activities against carbapenem-resistant Enterobacterales (CREs). Starting from a reported tricyclic ß-lactam that combined the cephalosporin skeleton having a γ-lactone ring with a carboxylic acid group, which was reported as a unique partial structure of Lactivicin, we identified the compound which shows potent antibacterial activities against all tested CREs by introducing sulfoxide. In addition, the sulfoxide-introduced tricyclic ß-lactam also shows a strong therapeutic efficacy in the neutropenic mouse lung infection model. These results indicate that the tricyclic ß-lactam skeleton will show sufficient therapeutic performance in clinical use and therefore can serve as a scaffold in the search for new antibacterial agents against CREs.
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Base de dados:
MEDLINE
Assunto principal:
Carbapenêmicos
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Farmacorresistência Bacteriana
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Beta-Lactamas
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Enterobacteriaceae
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Antibacterianos
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article