Synthesis and biological evaluation of novel N, N'-diarylurea derivatives as potent antibacterial agents against MRSA

Bioorg Med Chem Lett. 2022 Nov 1:75:128975. doi: 10.1016/j.bmcl.2022.128975.

Xiaonan Du ¹, Minghua Wang ¹, Xinxin Hu ¹, Tongying Nie ¹, Mei Zhu ¹, Guoning Zhang ², Xuefu You ³, Yucheng Wang ⁴

Affiliations

1 Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
2 Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China. Electronic address: zhangguoning@imb.pumc.edu.cn.
3 Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China. Electronic address: xuefuyou@imb.pumc.edu.cn.
4 Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China. Electronic address: wangyucheng@imb.pumc.edu.cn.

PMID: 36067930 DOI: 10.1016/j.bmcl.2022.128975

Abstract

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.

Keywords

Antibacterial; MRSA; N, N’-diarylurea; Structure-activity relationship.

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