Document Report Card

Basic Information

ID: ALA4808247

Journal: Bioorg Med Chem

Title: A novel tricyclic β-lactam exhibiting potent antibacterial activities against carbapenem-resistant Enterobacterales: Synthesis and structure-activity-relationships.

Authors: Sato J, Kusano H, Aoki T, Shibuya S, Yokoo K, Komano K, Oguma T, Matsumoto S, Sato T, Yasuo K, Yamawaki K.

Abstract: A series of tricyclic β-lactams were synthesized and evaluated for in vitro antibacterial activities against carbapenem-resistant Enterobacterales (CREs). Starting from a reported tricyclic β-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 β-lactam also shows a strong therapeutic efficacy in the neutropenic mouse lung infection model. These results indicate that the tricyclic β-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.

CiteXplore: 34450571

DOI: 10.1016/j.bmc.2021.116343