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.
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