N-Arylimidazoliums as Highly Selective Biomimetic Antimicrobial Agents,Journal of Medicinal Chemistry

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N-Arylimidazoliums as Highly Selective Biomimetic Antimicrobial Agents
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2022-08-05 , DOI: 10.1021/acs.jmedchem.2c00818
Qunshou Kong ₁ , Gaocan Li ₁ , Fanjun Zhang ₁ , Tao Yu ₁ , Xiaotong Chen ₁ , Qing Jiang ₁ , Yunbing Wang ₁

Affiliation

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.

中文翻译：

N-芳基咪唑作为高选择性仿生抗菌剂

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，针对抗菌肽 (AMP) 模拟物描述了电荷分散二聚化策略，通过可调阳离子电荷来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N-芳基咪唑骨架的电荷分散 AMP 模拟物得到证明。这些N -arylimidazolium AMP 模拟物显示出对菌株的有效抗菌活性以及低耐药率、良好的血液相容性和低细胞毒性。除了消除浮游细菌外，N-arylimidazolium AMP 模拟物还可以抑制生物膜形成并破坏已建立的生物膜。更重要的是，耐甲氧西林金黄色葡萄球菌(MRSA) 诱导的肺部感染小鼠可以通过静脉注射N-芳基咪唑 AMP 模拟物进行有效治疗，这使得N-芳基咪唑 AMP 模拟物的设计成为根除药物的替代途径- 耐药细菌感染。

更新日期：2022-08-05

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