title: Synthesis, molecular docking and biological evaluation of metronidazole derivatives containing piperazine skeleton as potential antibacterial agents.
abstract: Metronidazole has a broad-spectrum antibacterial activity. Hereby a series of novel metronidazole derivatives were designed and synthesized based on nitroimidazole scaffold in order to find some more potent antibacterial drugs. For these compounds which were reported for the first time, their antibacterial activities against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and Staphylococcus aureus were tested. These compounds showed good antibacterial activities against Gram-positive strains. Compound 4m represented the most potent antibacterial activity against S. aureus ATCC 25923 with MIC of 0.003 μg/mL and it showed the most potent activity against S. aureus TyrRS with IC50 of 0.0024 μM. Molecular docking of 4m into S. aureus tyrosyl-tRNA synthetase active site were also performed to determine the probable binding mode.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: She-Feng
authors.initials: SF
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yin
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Fang
authors.initials: F
authors.lastname: Qiao
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Xun
authors.initials: X
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Shao
authors.initials: S
authors.lastname: Sha
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China. Electronic address: zhuhl@nju.edu.cn.
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D020134:Catalytic Domain; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008795:Metronidazole / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D000077489:Piperazine; D010879:Piperazines / Q000737:chemistry*; D014448:Tyrosine-tRNA Ligase / Q000737:chemistry / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D010879:Piperazines; D008795:Metronidazole; D000077489:Piperazine; D014448:Tyrosine-tRNA Ligase
keywords: Antibacterial activities; Metronidazole derivatives; Molecular docking; S. aureus TyrRS