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.