title: Design, synthesis and biological evaluation of metronidazole-thiazole derivatives as antibacterial inhibitors.
abstract: A series of metronidazole–thiazole derivatives has been designed, synthesized and evaluated as potential antibacterial inhibitors. All the synthesized compounds were determined by elemental analysis, (1)H NMR and MS. They were also tested for antibacterial activity against Escherichia coli, Bacillus thuringiensis, Bacillus subtilis and Pseudomonas aeruginosa as well as for the inhibition to FabH. The results showed that compound 5 e exhibited the most potent inhibitory activity against E. coli FabH with IC50 of 4.9 lM. Molecular modeling simulation studies were performed in order to predict the biological activity of proposed compounds. Toxicity assay of compounds 5 a, 5 b, 5 d, 5 e, 5 g and 5 i showed that they were noncytotoxic against human macrophage. The results revealed that these compounds offered remarkable viability.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science Nanjing University, Nanjing 210093, People’s Republic of China.
authors.forename: Ya-Juan
authors.initials: YJ
authors.lastname: Qin
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Wang
authors.forename: Jigar A
authors.initials: JA
authors.lastname: Makawana
authors.forename: Zhong-Chang
authors.initials: ZC
authors.lastname: Wang
authors.forename: Ze-Nan
authors.initials: ZN
authors.lastname: Wang
authors.lastname: Yan-Gu
authors.forename: Ai-Qin
authors.initials: AQ
authors.lastname: Jiang
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase; D000123:Acetyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D054889:Fatty Acid Synthase, Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006801:Humans; D008795:Metronidazole / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D017434:Protein Structure, Tertiary; D013844:Thiazoles / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D029968:Escherichia coli Proteins; D013844:Thiazoles; D008795:Metronidazole; D000123:Acetyltransferases; C557158:fabH protein, E coli; D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase; D054889:Fatty Acid Synthase, Type II