<i>N</i>-Arylimidazoliums as Highly Selective Biomimetic Antimicrobial Agents.
Kong Q, Li G, Zhang F, Yu T, Chen X, Jiang Q, Wang Y.
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 <i>N</i>-arylimidazolium skeletons. These <i>N</i>-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, <i>N</i>-arylimidazolium AMP mimics can also inhibit biofilm formation and destroy the established biofilm. More importantly, methicillin-resistant <i>Staphylococcus aureus</i> (MRSA)-induced lung-infected mice can be effectively treated by the intravenous administration of <i>N</i>-arylimidazolium AMP mimic, which enable the design of <i>N</i>-arylimidazolium AMP mimics to offer an alternative avenue to eradicate drug-resistant bacterial infection.