含酰胺侧链的截短侧耳素衍生物的设计、合成、抗菌活性评价及分子对接研究。
Design, synthesis, antibacterial activity evaluation and molecular docking study of pleuromutilin derivatives bearing amide side chains.
机构信息
The Center for Combinatorial Chemistry and Drug Discovery of Jilin University, The School of Pharmaceutical Sciences, Jilin University, Changchun, China.
Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
出版信息
Chem Biol Drug Des. 2022 Oct;100(4):564-579. doi: 10.1111/cbdd.14106. Epub 2022 Jul 1.
A seize of pleuromutilin derivatives containing amide side chains were designed and synthesized as potential antibiotics against Methicillin-resistant Staphylococcus aureus (MRSA). Among all target compounds (compounds 11-30), compound 25 was found to have the strongest antibacterial activity against MRSA (minimum inhibitory concentration = 0.5 μg/ml). The result of the time-kill curves indicated that compound 25 could repress the growth of MRSA in vitro obviously (-3.72 log CFU/ml reduction). Furthermore, molecular docking studies demonstrated that compound 25 was localized in the binding pocket of 50S ribosomal subunit (ΔGb = -8.99 kcal/mol). Besides, compound 25 displayed low cytotoxicity to RAW 264.7 cells. The results suggested that compound 25 might be further developed into a novel antimicrobial agent against MRSA.
设计并合成了一系列含有酰胺侧链的截短侧耳素衍生物，作为潜在的抗耐甲氧西林金黄色葡萄球菌（MRSA）抗生素。在所有目标化合物（化合物 11-30）中，化合物 25 对 MRSA 的抗菌活性最强（最低抑菌浓度=0.5μg/ml）。时间杀伤曲线的结果表明，化合物 25 能明显抑制 MRSA 的体外生长（减少-3.72 log CFU/ml）。此外，分子对接研究表明，化合物 25 定位于 50S 核糖体亚基的结合口袋中（ΔGb=-8.99 kcal/mol）。此外，化合物 25 对 RAW 264.7 细胞的细胞毒性较低。结果表明，化合物 25 可能被进一步开发为一种新型的抗 MRSA 抗菌药物。
Zotero 插件