title: Design and synthesis of potent inhibitors of beta-ketoacyl-acyl carrier protein synthase III (FabH) as potential antibacterial agents.
abstract: Twenty new Schiff bases were synthesized by reacting 5-fluoro-salicylaldehyde and primary amine as potent inhibitors of FabH. These compounds were assayed for antibacterial activity against Escherichia coli, Pseudomonas fluorescence, Bacillus subtilis and Staphylococcus aureus. Compounds with potent antibacterial activities were tested for their E. coli FabH inhibitory activity. (E)-4-fluoro-2-((4-hydroxyphenethylimino)methyl)phenol (10) showed the most potent antibacterial activity with MIC of 1.56-6.25 microg/mL against the tested bacterial strains and exhibited the most potent E. coli FabH inhibitory activity with IC(50) of 2.7 microM. Docking simulation was performed to position compound 10 into the E. coli FabH active site to determine the probable binding conformation.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Rui-Qin
authors.initials: RQ
authors.lastname: Fang
authors.forename: Zhen-Wei
authors.initials: ZW
authors.lastname: Zhu
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.forename: Kui
authors.initials: K
authors.lastname: Cheng
authors.forename: Wei-Qing
authors.initials: WQ
authors.lastname: Zhong
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000447:Aldehydes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D008958:Models, Molecular
chemical_list: D000447:Aldehydes; D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; C013243:salicylaldehyde; C077402:3-ketoacyl-acyl carrier protein synthase III; D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase