Metronidazole containing pyrazole derivatives potently inhibit tyrosyl-tRNA synthetase:design, synthesis, and biological evaluation

摘要：

　　As an important enzyme in bacterial protein biosynthesis,tyrosyl-tRNA synthetase(TyrRS)has been an absorbing therapeutic target for exploring novel antibacterial agents.A series of metronidazole-based antibacterial agents has been synthesized and identified as TyrRS inhibitors with low cytotoxicity and significant antibacterial activity,especially against Gram-negative organisms.Of the compounds obtained,4f is the most potent agent which inhibited the growth of Pseudomonas aeruginosa ATCC 13525(MIC = 0.98 μg/mL)and exhibited TryRS inhibitory activity(IC50 = 0.92 μm).Docking simulation was performed to further understand its potency.Membrane-mediated apoptosis in P.aeruginosa was verified by flow cytometry.

关键词： antibacterial agent apoptosis docking simulation Pseudomonas aeruginosa tyrosyl-tRNA synthetase

作者: Long-Wang Chen Peng-Fei Wang Dan-Jie Tang Xiang-Xiang Tao Ruo-Jun Man Han-Yue Qiu Zhong-Chang Wang Chen Xu Hai-Liang Zhu

作者单位: State Key Laboratory of Pharmaceutical Biotechnology,Nanjing University,Nanjing,China

会议类型: 国内会议

会议名称: 第九届国际分子模拟与信息技术应用学术会议(ICMS&I2018)

会议地点: 太原

会议语种:英文

页码: 444-450

在线出版日期: 2018-05-01（万方平台首次上网日期，不代表论文的发表时间）