title: Design, synthesis and biological evaluation of urea derivatives from o-hydroxybenzylamines and phenylisocyanate as potential FabH inhibitors.
abstract: FabH, β-ketoacyl-acyl carrier protein (ACP) synthase III, is a particularly attractive target, since it is central to the initiation of fatty acid biosynthesis and is highly conserved among Gram-positive and Gram-negative bacteria. A series of o-hydroxybenzylamines 1-16 and its corresponding new urea derivatives 17-32 were synthesized and fully characterized by spectroscopic methods and elemental analysis. This new urea derivatives class demonstrates strong antibacterial activity. Escherichia coli FabH inhibitory assay and docking simulation indicated that the compounds 1-(5-bromo-2-hydroxybenzyl)-1-(4-fluorophenyl)-3-phenylurea (18) and 1-(5-bromo-2-hydroxybenzyl)-1-(4-chlorophenyl)-3-phenylurea (20) were potent inhibitors of E. coli FabH.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
authors.forename: Zi-Lin
authors.initials: ZL
authors.lastname: Li
authors.forename: Qing-Shan
authors.initials: QS
authors.lastname: Li
authors.forename: Hong-Jia
authors.initials: HJ
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Hu
authors.forename: Di-Di
authors.initials: DD
authors.lastname: Zhu
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000201:enzymology*; D001424:Bacterial Infections / Q000188:drug therapy / Q000201:enzymology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000201:enzymology; D006090:Gram-Negative Bacteria; D006801:Humans; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D011485:Protein Binding; D014508:Urea / Q000031:analogs & derivatives*
chemical_list: D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D014508:Urea; C077402:3-ketoacyl-acyl carrier protein synthase III; D015099:3-Oxoacyl-(Acyl-Carrier-Protein) Synthase