National Engineering Research Center for Biomaterials, Sichuan University, 29 Wangjiang Road, Chengdu 610064, China.
J Med Chem. 2022 Aug 25;65(16):11309-11321. doi: 10.1021/acs.jmedchem.2c00818. Epub 2022 Aug 5.
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 -arylimidazolium skeletons. These -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, -arylimidazolium AMP mimics can also inhibit biofilm formation and destroy the established biofilm. More importantly, methicillin-resistant (MRSA)-induced lung-infected mice can be effectively treated by the intravenous administration of -arylimidazolium AMP mimic, which enable the design of -arylimidazolium AMP mimics to offer an alternative avenue to eradicate drug-resistant bacterial infection.
抗生素耐药性已成为世界上最大的健康威胁之一。在这项研究中，通过可调阳离子电荷描述了一种用于抗菌肽（AMP）模拟物的电荷分散二聚策略，以提高原核微生物和真核细胞之间的选择性。该策略通过一系列基于芳基咪唑鎓骨架的电荷分散 AMP 模拟物得到证明。这些芳基咪唑鎓 AMP 模拟物对菌株表现出强大的抗菌活性，耐药率低，良好的血液相容性和低细胞毒性。除了消除浮游细菌外，芳基咪唑鎓 AMP 模拟物还可以抑制生物膜的形成并破坏已建立的生物膜。更重要的是，静脉注射芳基咪唑鎓 AMP 模拟物可以有效治疗耐甲氧西林金黄色葡萄球菌（MRSA）引起的肺部感染小鼠，这使得设计芳基咪唑鎓 AMP 模拟物成为消除耐药性细菌感染的另一种途径。
