title: Synthesis and antibacterial activity of cinnamaldehyde acylhydrazone with a 1,4-benzodioxan fragment as a novel class of potent β-ketoacyl-acyl carrier protein synthase III (FabH) inhibitor.
abstract: Fatty acid biosynthesis is essential for bacterial survival. β-Ketoacyl-acyl carrier protein (ACP) synthase III (FabH), is a particularly attractive antibacterial target, since it is central to the initiation of fatty acid biosynthesis. Three series of 21 cinnamaldehyde acylhydrazone derivatives, A3-9, B3-9, and C3-9, were synthesized and evaluated for FabH-inhibitory activity. Compound B6 showed the most potent biological activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis (minimum inhibitory concentrations (MICs) values: 1.56-3.13 µg/mL) and was comparable with the positive control. Docking simulation by positioning compound B6 in the FabH structure active site was performed to explore the possible binding model.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University.
authors.forename: Xiaoda
authors.initials: X
authors.lastname: Song
authors.forename: Yushun
authors.initials: Y
authors.lastname: Yang
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Yangjian
authors.initials: Y
authors.lastname: Chen
mesh_terms: D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000171:Acrolein / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects / Q000201:enzymology; D001419:Bacteria / Q000187:drug effects* / Q000201:enzymology*; D001424:Bacterial Infections / Q000188:drug therapy / Q000201:enzymology / Q000382:microbiology; D004146:Dioxanes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D062105:Molecular Docking Simulation; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D004146:Dioxanes; D004791:Enzyme Inhibitors; D006835:Hydrazones; D000171:Acrolein; C077402:3-ketoacyl-acyl carrier protein synthase III; D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase; C012843:cinnamaldehyde; C527681:1,4-benzodioxan