Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou, China.
J Enzyme Inhib Med Chem. 2022 Dec;37(1):2078-2091. doi: 10.1080/14756366.2022.2104267.
A series of pleuromutilin derivatives containing alkylamine and nitrogen heterocycle groups were designed and synthesised under mild conditions. The antibacterial activity of these semisynthetic derivatives against four strains of (MRSA ATCC 43300, ATCC 29213, AD3, and 144) were evaluated by the broth dilution method. Compound was found to have excellent antibacterial activity against MRSA (MIC = 0.0625 μg/mL). Furthermore, compound was further studied by the time-killing kinetics and the post-antibiotic effect approach. In the mouse thigh infection model, compound exhibited superior antibacterial efficacy than that of tiamulin. Meanwhile, compound showed a lower inhibitory effect than that of tiamulin on RAW264.7 and 16HBE cells at the concentration of 10 μg/mL. Molecular docking study revealed that compound can effectively bind to the active site of the 50S ribosome (the binding free energy = -9.66 kcal/mol).
在温和的条件下，设计并合成了一系列含有烷基胺和氮杂环基团的截短侧耳素衍生物。采用肉汤稀释法评价了这些半合成衍生物对 4 株 （MRSA ATCC 43300、ATCC 29213、AD3 和 144）的抗菌活性。化合物 对 MRSA 具有优异的抗菌活性（MIC = 0.0625 μg/mL）。此外，还通过时间杀伤动力学和抗生素后效应方法进一步研究了化合物 。在小鼠大腿感染模型中，化合物 的抗菌效果优于泰妙菌素。同时，在 10 μg/mL 浓度下，化合物 对 RAW264.7 和 16HBE 细胞的抑制作用低于泰妙菌素。分子对接研究表明，化合物 可有效结合到 50S 核糖体的活性部位（结合自由能 = -9.66 kcal/mol）。
