Development of Bis-cyclic Imidazolidine-4-one Derivatives as Potent Antibacterial Agents.

ABSTRACT: 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.

SUBMITTER: Wang M 

PROVIDER: S-EPMC8903082 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature