N‑Arylimidazoliums as Highly Selective Biomimetic Antimicrobial Agents

• Published in: Journal of medicinal chemistry Vol. 65; no. 16; pp. 11309 - 11321
• Main Authors: Kong, Qunshou, Li, Gaocan, Zhang, Fanjun, Yu, Tao, Chen, Xiaotong, Jiang, Qing, Wang, Yunbing
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 25-08-2022
• Subjects: Animals; Anti-Bacterial Agents - pharmacology; Anti-Infective Agents - pharmacology; Biofilms; Biomimetics; Methicillin-Resistant Staphylococcus aureus; Mice; Microbial Sensitivity Tests
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/acs.jmedchem.2c00818

Antibiotic resistance has become one of the greatest health threats in the world. In this study, a charge-dispersed dimerization strategy is described for the antimicrobial peptide (AMP) mimics via a tunable cationic charge to improve the selectivity between prokaryotic microbes and eukaryotic cells. This strategy is demonstrated with a series of charge-dispersed AMP mimics based on N-arylimidazolium skeletons. These N-arylimidazolium AMP mimics show potent antibacterial activity against strains along with a low rate of drug resistance, good hemocompatibility, and low cytotoxicity. In addition to the elimination of planktonic bacteria, N-arylimidazolium AMP mimics can also inhibit biofilm formation and destroy the established biofilm. More importantly, methicillin-resistant Staphylococcus aureus (MRSA)-induced lung-infected mice can be effectively treated by the intravenous administration of N-arylimidazolium AMP mimic, which enable the design of N-arylimidazolium AMP mimics to offer an alternative avenue to eradicate drug-resistant bacterial infection.