Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.
Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China.
Eur J Med Chem. 2017 Feb 15;127:286-295. doi: 10.1016/j.ejmech.2017.01.004. Epub 2017 Jan 3.
A series of pleuromutilin derivatives bearing piperazine ring have been reported. The in vitro antibacterial activities of the synthetic derivatives against MRSA (ATCC 43300), Staphylococcus aureus (ATCC 29213), Enterococcus faecalis (ATCC 29212), Enterococcus faecium (ATCC35667) and Escherichia coli (ATCC25922) were evaluated by the broth dilution method. Most of the synthesized derivatives displayed potent activities. Compounds 11c, 12a and 12c were found to be the most active antibacterial derivatives against MRSA (minimum inhibitory concentration = 0.015 μg/mL). The binding of compounds 11c, 12a and 12c to the 50s ribosome were investigated by molecular modeling. Compound 11c possessed lower binding free energy compared with compounds 12a and 12c. Compound 11c was further evaluated in MRSA systemic infection model and displayed superior in vivo efficacy to that of tiamulin.
已经报道了一系列含有哌嗪环的截短侧耳素衍生物。采用肉汤稀释法评估了合成衍生物对耐甲氧西林金黄色葡萄球菌（ATCC 43300）、金黄色葡萄球菌（ATCC 29213）、粪肠球菌（ATCC 29212）、屎肠球菌（ATCC35667）和大肠杆菌（ATCC25922）的体外抗菌活性。大多数合成衍生物表现出很强的活性。化合物 11c、12a 和 12c 被发现是对 MRSA（最小抑菌浓度 = 0.015 μg/mL）最有效的抗菌衍生物。通过分子模拟研究了化合物 11c、12a 和 12c 与 50s 核糖体的结合。与化合物 12a 和 12c 相比，化合物 11c 具有较低的结合自由能。进一步在 MRSA 全身感染模型中评价了化合物 11c，其体内疗效优于泰妙菌素。
