Metronidazole containing pyrazole derivatives potently inhibit tyrosyl-tRNA synthetase:design,synthesis,and biological evaluation
As an important enzyme in bacterial protein biosynthesis,tyrosyl-tRNA synthetase(TyrRS)has been an absorbing therapeutic target tor 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.
antibacterial agent apoptosis docking simulation Pseudomonas aeruginosa tyrosyl-tRNA synthetase
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
State Key Laboratory of Pharmaceutical Bioreclmology,Nanjing University,Nanjing,China
国内会议
大连
英文
536-542
2016-09-24（万方平台首次上网日期，不代表论文的发表时间）