Development of Membrane-Active Honokiol/Magnolol Amphiphiles as Potent Antibacterial Agents against Methicillin-Resistant <i>Staphylococcus aureus</i> (MRSA)
作者:Yong Guo、Enhua Hou、Tingyu Wen、Xiaoting Yan、Meiyue Han、Li-Ping Bai、Xiangjing Fu、Jifeng Liu、Shangshang Qin
DOI:10.1021/acs.jmedchem.1c01073
日期:2021.9.9
of novel honokiol/magnolol amphiphiles were prepared by mimicking the chemical structures and antibacterial properties of cationic antimicrobial peptides. Among them, compound 5i showed excellent antibacterial activity against Gram-positive bacteria and clinical MRSA isolates (minimum inhibitory concentrations (MICs) = 0.5–2 μg/mL) with low hemolytic and cytotoxic activities and high membrane selectivity
目前,耐药菌引起的感染已成为抗感染治疗的新挑战,严重危害公众健康。在我们不断努力开发新的抗菌剂的过程中,通过模拟阳离子抗菌肽的化学结构和抗菌特性,制备了一系列新型和厚朴酚/厚朴酚两亲物。其中,化合物5i对革兰氏阳性菌和临床MRSA分离株表现出优异的抗菌活性(最低抑菌浓度(MICs)= 0.5-2 μg/mL),具有低溶血和细胞毒活性以及高膜选择性。此外,5i表现出快速杀菌特性,低耐药频率和良好的破坏细菌生物膜的能力。机理研究表明5i破坏细菌细胞膜,导致细菌死亡。此外,5i在鼠败血症模型中显示出高生物安全性和有效的体内抗感染效力。我们的研究表明,这些和厚朴酚/厚朴酚两亲物为开发新型抗菌剂提供了启示,5i是对抗 MRSA 感染的潜在抗菌候选物。