金黄色葡萄球菌
抗菌剂
耐甲氧西林金黄色葡萄球菌
化学
心磷脂
微生物学
磷脂酰甘油
肽
生物膜
脂质Ⅱ
抗菌肽
抗生素
体内
肽聚糖
细菌
膜
生物化学
磷脂
生物
细胞壁
磷脂酰胆碱
生物技术
遗传学
作者
Ruige Yang,Enhua Hou,Wanqing Cheng,Xiaoting Yan,Tingting Zhang,Shihong Li,Hong Yao,Jifeng Liu,Yong Guo
标识
DOI:10.1021/acs.jmedchem.2c01674
摘要
Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) continue to endanger public health. Here, we report the synthesis of neolignan isomagnolone (I) and its isomer II, and the preparation of a series of novel neolignan-antimicrobial peptide (AMP) mimic conjugates. Notably, conjugates III5 and III15 exhibit potent anti-MRSA activity in vitro and in vivo, comparable to that of vancomycin, a current effective treatment for MRSA. Moreover, III5 and III15 display not only fast-killing kinetics and low resistance frequency but also low toxicity as well as effects on bacterial biofilms. Mechanism studies reveal that III5 and III15 exhibit rapid bactericidal effects through binding to the phosphatidylglycerol (PG) and cardiolipin (CL) of the bacterial membrane, thereby disrupting the cell membranes and allowing increased reactive oxygen species (ROS) as well as protein and DNA leakage. The results indicate that these neolignan-AMP mimic conjugates could be promising antimicrobial candidates for combating MRSA infections.
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