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Metronidazole containing pyrazole derivatives potently inhibit tyrosyl‐tRNA synthetase: design, synthesis, and biological evaluation
Author(s) -
Chen LongWang,
Wang PengFei,
Tang DanJie,
Tao XiangXiang,
Man RuoJun,
Qiu HanYue,
Wang ZhongChang,
Xu Chen,
Zhu HaiLiang
Publication year - 2016
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.12793
Subject(s) - antibacterial activity , cytotoxicity , docking (animal) , enzyme , chemistry , biochemistry , flow cytometry , potency , pyrazole , minimum inhibitory concentration , in vitro , stereochemistry , bacteria , biology , microbiology and biotechnology , medicine , genetics , nursing
As an important enzyme in bacterial protein biosynthesis, tyrosyl‐t RNA synthetase ( T yr RS ) has been an absorbing therapeutic target for exploring novel antibacterial agents. A series of metronidazole‐based antibacterial agents has been synthesized and identified as T yr RS 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 P seudomonas aeruginosa ATCC 13525 ( MIC = 0.98 μ g/mL) and exhibited T ry RS inhibitory activity ( IC 50 = 0.92 μ m ). Docking simulation was performed to further understand its potency. Membrane‐mediated apoptosis in P . aeruginosa was verified by flow cytometry.