New antimicrobial agents are urgently needed to overcome drug-resistant bacterial infections. Here we describe the design, synthesis and evaluation of a new class of amphiphilic sofalcone compounds as antimicrobial peptidomimetics. The most promising compound 14, bearing two arginine residues, showed poor hemolytic activity, low cytotoxicity, and excellent antimicrobial activity against Gram-positive bacteria, including MRSA. Compound 14, had good stability in various salt conditions, killed bacteria rapidly by directly disrupting bacterial cell membranes and was slow at developing bacterial resistance. Additionally, compound 14 exhibited effective in vivo efficacy in the murine model of bacterial keratitis caused by Staphylococcus aureus ATCC29213. Our studies suggested that compound 14 possessed promising potential to be used as a novel antimicrobial agent to combat drug-resistant Gram-positive bacteria.

迫切需要新的抗菌剂来克服耐药细菌感染。在这里，我们描述了作为抗菌肽模拟物的一类新的两亲soficone化合物的设计，合成和评估。具有两个精氨酸残基的最有前途的化合物14表现出较差的溶血活性，低细胞毒性和对革兰氏阳性细菌（包括MRSA）的优异抗菌活性。化合物14在各种盐条件下均具有良好的稳定性，可通过直接破坏细菌细胞膜迅速杀死细菌，并且对细菌的耐药性发展较慢。另外，化合物14在由以下原因引起的细菌性角膜炎的鼠模型中显示出有效的体内功效。金黄色葡萄球菌ATCC29213。我们的研究表明，化合物14具有潜在的潜力，可以用作对抗耐药革兰氏阳性细菌的新型抗菌剂。