Work

2‐Carboxyquinoline Boronic Acids as Highly Potent KPC Inhibitors

Year: 2024

Type: article

Abstract: The expression of Klebsiella pneumoniae carbapenemase (KPC), a type of carbapenem‐hydrolyzing β‐lactamase, in Gram‐negative bacteria has caused significant bacterial resistance to carbapenems, the antibiotic of last resort. Herein, we describe the discovery of 2‐carboxyquinoline boronic acids as inhibitor of KPC. We have identified fluoro‐substituted carboxyquinoline boronic acids 1 e as the most potent inhibitor, with an IC 50 of 8.3 nM for KPC‐2, while this compound is significantly less efficient at reducing the activity of other β‐lactamases. This compound proved to have low cytotoxicity towards mammalian cells, as well as low haemolysis and antibacterial activity. However, 1 e potentiated the efficacy of β‐lactam antibiotics (e. g., meropenem and ceftazidime) against KPC‐2‐expressing resistant Klebsiella pneumonia by up to 256‐fold.

Source: ChemMedChem

DOI: 10.1002/cmdc.202400901

Authors: Zheng Ma, Ge Cui, Lijie Dou, Fangfang Chen, Hexin Xie

Institutions: East China University of Science and Technology, State Key Laboratory of Bioreactor Engineering

Language: English

Topic: Antibiotic Resistance in Bacteria

Subfield: Molecular Medicine

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: bronze

Funders: National Natural Science Foundation of China, Shanghai Municipal Education Commission, Fundamental Research Funds for the Central Universities