Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, PR China.
Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, PR China.
Eur J Med Chem. 2020 Sep 15;202:112596. doi: 10.1016/j.ejmech.2020.112596. Epub 2020 Jul 8.
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.
急需新的抗菌药物来克服耐药细菌感染。在这里，我们描述了一类新的两亲性角鲨烯化合物的设计、合成和评估，作为抗菌肽模拟物。最有前途的化合物 14 含有两个精氨酸残基，表现出低溶血活性、低细胞毒性和对革兰氏阳性菌（包括耐甲氧西林金黄色葡萄球菌）的优异抗菌活性。化合物 14 在各种盐条件下具有良好的稳定性，通过直接破坏细菌细胞膜迅速杀死细菌，并且细菌耐药性发展缓慢。此外，化合物 14 在金黄色葡萄球菌 ATCC29213 引起的细菌性角膜炎的小鼠模型中表现出有效的体内疗效。我们的研究表明，化合物 14 具有作为一种新型抗菌药物用于对抗耐药革兰氏阳性菌的潜在前景。
