title: Design, synthesis and molecular docking of salicylic acid derivatives containing metronidazole as a new class of antimicrobial agents.
abstract: A series of novel salicylic acid derivatives containing metronidazole as Staphylococcus aureus Tyrosyl-tRNA synthetase (TyrRS) inhibitors have been synthesized and evaluated their biology activities as potential antibacterial agents. Among these compounds, compound 5r exhibited the most potent antibacterial activity against Gram-positive (S. aureus ATCC 6538 and Bacillus subtilis ATCC 6633) and Gram-negative (Escherichia coli ATCC 35218 and Pseudomonas aeruginosa ATCC 13525) with MICs of 0.39-1.57 μg/mL and showed the most potent S. aureus Tyrosyl-tRNA synthetase inhibitory with 2.3 μM. Docking simulation was performed to insert compound 5r into the crystal structure of S. aureus Tyrosyl-tRNA synthetase active site to determine the probable binding model. These results suggested that compound 5r may be a promising antibacterial agent.
authors: College of Biology and Food Engineering, SuZhou University, Suzhou 234000, People's Republic of China; State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors: Zhi-Hua
authors: ZH
authors: Guo
authors: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors: Yong
authors: Y
authors: Yin
authors: College of Biology and Food Engineering, SuZhou University, Suzhou 234000, People's Republic of China.
authors: Cong
authors: C
authors: Wang
authors: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors: Peng-Fei
authors: PF
authors: Wang
authors: College of Biology and Food Engineering, SuZhou University, Suzhou 234000, People's Republic of China.
authors: Xing-Tao
authors: XT
authors: Zhang
authors: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors: Zhong-Chang
authors: ZC
authors: Wang
authors: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China. Electronic address: zhuhl@nju.edu.cn.
authors: Hai-Liang
authors: HL
authors: Zhu
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D001665:Binding Sites; D018360:Crystallography, X-Ray; D015195:Drug Design; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008795:Metronidazole / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D017434:Protein Structure, Tertiary; D012459:Salicylates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000201:enzymology; D013329:Structure-Activity Relationship; D014448:Tyrosine-tRNA Ligase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D012459:Salicylates; D008795:Metronidazole; D014448:Tyrosine-tRNA Ligase
keywords: Antibacterial activity; Molecular docking; S. aureus TyrRS; Salicylic acid derivatives