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.
Biochim Biophys Acta Biomembr. 2020 Sep 1;1862(9):183353. doi: 10.1016/j.bbamem.2020.183353. Epub 2020 May 11.
Semisynthetic γ-mangostin derivative LS02 is a novel cationic amphiphilic peptidomimetic antimicrobial agent containing a hydrophobic scaffold and three hydrophilic and positively charged residues of arginine. LS02 showed low in vitro toxicity, potent activities against Gram-positive bacteria including MRSA (MIC = 1.56-6.25 μg/mL) and avoidance of drug resistance. The mode of action studies indicated that LS02 killed bacteria by disrupting bacterial cell membranes. LS02 not only exhibited good water solubility, low hemolytic activity and cell cytotoxicity, but also displayed excellent in vitro and in vivo antibacterial activity, indicating its great potential of being a lead compound as a novel membrane-active antibacterial agent capable of combating bacterial resistance.
半合成 γ-倒捻子素衍生物 LS02 是一种新型的阳离子两亲肽类抗菌剂，含有疏水支架和三个亲水带正电荷的精氨酸残基。LS02 显示出较低的体外毒性，对革兰氏阳性菌（包括耐甲氧西林金黄色葡萄球菌，MIC=1.56-6.25μg/ml）具有强大的活性，并且能够避免耐药性的产生。作用机制研究表明，LS02 通过破坏细菌细胞膜来杀死细菌。LS02 不仅表现出良好的水溶性、低溶血活性和细胞毒性，还显示出优异的体外和体内抗菌活性，表明其作为一种新型的膜活性抗菌剂，具有克服细菌耐药性的巨大潜力，有希望成为一种先导化合物。
