咪唑啉
细菌
抗生素
化学
抗生素耐药性
抗药性
革兰氏阴性菌
抗菌剂
多重耐药
药品
药物发现
微生物学
组合化学
药理学
生物化学
生物
立体化学
大肠杆菌
有机化学
基因
遗传学
作者
Minghui Wang,Ruixuan Gao,Mengmeng Zheng,Peng Sang,Chunpu Li,En Zhang,Qi Li,Jianfeng Cai
标识
DOI:10.1021/acs.jmedchem.0c00171
摘要
Antibiotic resistance has emerged as one of the biggest public health concerns all over the world. In an effort to combat bacterial infections, a series of imidazolidine-4-one derivatives with potent and broad-spectrum antibacterial activity and low rates of drug resistance were developed by mimicking the salient physiochemical features of host defense peptides. These small molecules displayed potent activity against both Gram-negative and Gram-positive bacteria including several multidrug-resistant bacteria strains. Meanwhile, time-kill kinetics and drug resistance studies suggested that the most potent compound 3 could not only eliminate the bacteria rapidly but also exhibit a low probability of drug resistance in MRSA over many passages. Further mechanistic studies suggested that 3 eradicated bacterial pathogens by disintegrating membranes of both Gram-negative and Gram-positive bacteria. Together with their small molecular weight and low production cost compared with HDPs, these imidazolidine-4-one compounds may be developed into a new generation of antibiotic therapeutics combating emergent drug resistance.
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