title: Design, synthesis and antimicrobial activities evaluation of Schiff base derived from secnidazole derivatives as potential FabH inhibitors.
abstract: FabH, β-ketoacyl-acyl carrier protein (ACP) synthase III, is critically important to the initiation of fatty acid biosynthesis and is highly conserved among Gram-positive and Gram-negative bacteria. A series of novel secnidazole derivatives (1-20) were synthesized and fully characterized by spectroscopic methods and elemental analysis. Among these compounds, 6, 8, 11, 13, 14, 16-20 were reported for the first time. These compounds were tested for antibacterial activities against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and Staphylococcus aureus. The compounds inhibitory assay and docking simulation indicated that compound 20 (E)-2-(2-methyl-5-nitro-1H-imidazol-1-yl)-N'-(3,4,5-trimethylbenzylidene)acetohydrazide with MIC of 3.13-6.25 μg/mL against the tested bacterial strains was a potent inhibitor of Escherichia coli FabH.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Li
authors.forename: Chang-Po
authors.initials: CP
authors.lastname: Zhao
authors.forename: Hua-Ping
authors.initials: HP
authors.lastname: Ma
authors.forename: Meng-Yue
authors.initials: MY
authors.lastname: Zhao
authors.forename: Ya-Rong
authors.initials: YR
authors.lastname: Xue
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Wang
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase; D000123:Acetyltransferases / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D029968:Escherichia coli Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D054889:Fatty Acid Synthase, Type II / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D008795:Metronidazole / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D012545:Schiff Bases / Q000138:chemical synthesis* / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D029968:Escherichia coli Proteins; D012545:Schiff Bases; D008795:Metronidazole; D000123:Acetyltransferases; C557158:fabH protein, E coli; D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase; D054889:Fatty Acid Synthase, Type II; C016724:secnidazole