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. 2023 Dec;38(1):2251712. doi: 10.1080/14756366.2023.2251712.
A series of pleuromutilin analogs containing substituted benzoxazole were designed, synthesised, and assessed for their antibacterial activity both and . The MIC of the synthesised derivatives was initially assessed using the broth dilution method against four strains of (MRSA ATCC 43300, ATCC 29213, clinical isolation of AD3 and 144). Most of the synthesised derivatives displayed prominent activity (MIC ≤ 0.5 µg/mL). Compounds and exhibited the most effective antibacterial effect against MRSA (MIC = 0.125 µg/mL). Furthermore, the time-kill curves showed that compounds and had a certain inhibitory effect against MRSA . The antibacterial activity of compound was evaluated further using a murine thigh model infected with MRSA (-1.24 logCFU/mL). Compound exhibited superior antibacterial efficacy to tiamulin. It was also found that compound did not display significant inhibitory effect on the proliferation of RAW 264.7 cells. Molecular docking study revealed that compound can effectively bind to the active site of the 50S ribosome (the binding free energy -7.50 kcal/mol).
设计并合成了一系列含取代苯并恶唑的截短侧耳素类似物，并评估了它们的体外抗菌活性。采用肉汤稀释法，最初对 4 株 （MRSA ATCC 43300、 ATCC 29213、临床分离株 AD3 和 144）进行了合成衍生物的 MIC 评估。大多数合成衍生物表现出显著的 活性（MIC≤0.5μg/mL）。化合物 和 对 MRSA 表现出最有效的抗菌作用（MIC=0.125μg/mL）。此外，时间杀伤曲线表明，化合物 和 对 MRSA 具有一定的抑制作用。进一步采用 MRSA 感染的小鼠大腿模型评估化合物 的抗菌活性（-1.24 logCFU/mL）。化合物 对 MRSA 的抗菌效果优于泰妙菌素。还发现化合物 对 RAW 264.7 细胞的增殖没有明显的抑制作用。分子对接研究表明，化合物 可以有效地与 50S 核糖体的活性部位结合（结合自由能-7.50 kcal/mol）。
