Wu Guangxu, Zhu Zihao, Li Jishun, Luo Xinyu, Zhu Wenyong, Liao Guoyang, Xia Jie, Zhang Wenxuan, Pan Weidong, Li Tianlei, Wu Song
State Key Laboratory of Functions and Applications of Medicinal Plants/School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550025, China; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China.
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China.
Bioorg Med Chem. 2022 Apr 1;59:116676. doi: 10.1016/j.bmc.2022.116676. Epub 2022 Feb 23.
We report herein the design, synthesis, and structure-activity relationship studies of pleuromutilin derivatives containing urea/thiourea functionalities. The antibacterial activities of these new pleuromutilin derivatives were evaluated in vitro against Gram-positive pathogens (GPPs) (Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecium) and Mycoplasma pneumoniae by the broth dilution method. Most of the targeted compounds exhibit good potency in inhibiting the growth of pathogens including Methicillin-susceptible S. aureus (MSSA, ATCC29213, MIC: 0.0625-16 μg/mL), Methicillin-resistant S. aureus (MRSA, ATCC43300, MIC: 0.125-16 μg/mL) and M. pneumoniae (ATCC15531 MIC: 0.125-1 μg/mL, ATCC29342 MIC: 0.0625-0.25 μg/mL and drug resistant strain MIC: 0.5-2 μg/mL). In particular, the compounds 6m and 6n containing phenyl-urea group showed excellent activity with the MIC value less than 0.0625 μg/mL against S. aureus ATCC29213. The compound 6h exhibited better activity than tiamulin against Methicillin-resistant S. aureus ATCC43300.
本文报道了含尿素/硫脲官能团的截短侧耳素衍生物的设计、合成及构效关系研究。采用肉汤稀释法，在体外评估了这些新型截短侧耳素衍生物对革兰氏阳性病原体（GPPs）（金黄色葡萄球菌、表皮葡萄球菌和粪肠球菌）及肺炎支原体的抗菌活性。大多数目标化合物在抑制病原体生长方面表现出良好的效力，包括甲氧西林敏感金黄色葡萄球菌（MSSA，ATCC29213，MIC：0.0625 - 16μg/mL）、耐甲氧西林金黄色葡萄球菌（MRSA，ATCC43300，MIC：0.125 - 16μg/mL）以及肺炎支原体（ATCC15531 MIC：0.125 - 1μg/mL，ATCC29342 MIC：0.0625 - 0.25μg/mL和耐药菌株MIC：0.5 - 2μg/mL）。特别地，含苯基脲基团的化合物6m和6n对金黄色葡萄球菌ATCC29213表现出优异活性，MIC值小于0.0625μg/mL。化合物6h对耐甲氧西林金黄色葡萄球菌ATCC43300表现出比泰妙菌素更好的活性。
