新型 N,N'-二芳基脲衍生物的合成及作为抗耐甲氧西林金黄色葡萄球菌（MRSA）的有效抗菌剂的生物评价。
Synthesis and biological evaluation of novel N, N'-diarylurea derivatives as potent antibacterial agents against MRSA.
机构信息
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
出版信息
Bioorg Med Chem Lett. 2022 Nov 1;75:128975. doi: 10.1016/j.bmcl.2022.128975. Epub 2022 Sep 5.
A series of new N, N'-diarylurea derivatives were designed and synthesized, some of which exhibited potent antibacterial activity against the drug-susceptible and drug-resistant Gram-positive strains. Especially, compounds 2c, 2g-2l showed broader antibacterial spectrum and more potent antibacterial activity (MIC = 0.30-2.72 μM) against MRSA and MRSE than the control levofloxacin (MIC = 0.69-22.14 μM). In addition, compounds 2c, 2g, 2h and 2l exhibited much better antibacterial activity (MIC = 1.29-2.86 μM) against VRE (E. faecium) than sorafenib (MIC = 275.37 μM), PK150 (MIC = 5.07-10.13 μM) and SC78 (MIC = 2.40-4.79 μM). More importantly, the low cytotoxicity of compounds on cell lines HeLa and HepG2 implied a relatively wide therapeutic window, which was of high importance for further study.
一系列新的 N，N'-二芳基脲衍生物被设计和合成，其中一些表现出对敏感和耐药革兰氏阳性菌株的强大抗菌活性。特别是，化合物 2c、2g-2l 对 MRSA 和 MRSE 的抗菌谱更广，抗菌活性更强（MIC = 0.30-2.72 μM），优于对照左氧氟沙星（MIC = 0.69-22.14 μM）。此外，化合物 2c、2g、2h 和 2l 对 VRE（粪肠球菌）的抗菌活性（MIC = 1.29-2.86 μM）明显优于索拉非尼（MIC = 275.37 μM）、PK150（MIC = 5.07-10.13 μM）和 SC78（MIC = 2.40-4.79 μM）。更重要的是，化合物对 HeLa 和 HepG2 细胞系的低细胞毒性暗示了相对较宽的治疗窗口，这对于进一步的研究非常重要。
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