State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, People's Republic of China.
Bioorg Med Chem. 2011 Aug 1;19(15):4413-20. doi: 10.1016/j.bmc.2011.06.049. Epub 2011 Jun 25.
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.
FabH，β-酮酰基-酰基载体蛋白（ACP）合酶 III，是一个特别有吸引力的靶点，因为它是脂肪酸生物合成起始的核心，并且在革兰氏阳性菌和革兰氏阴性菌中高度保守。一系列邻-羟基苄基胺 1-16 和其相应的新型脲衍生物 17-32 通过光谱方法和元素分析进行了合成和充分的表征。这个新型脲衍生物类化合物表现出很强的抗菌活性。大肠杆菌 FabH 抑制测定和对接模拟表明，化合物 1-(5-溴-2-羟基苄基)-1-(4-氟苯基)-3-苯基脲（18）和 1-(5-溴-2-羟基苄基)-1-(4-氯苯基)-3-苯基脲（20）是大肠杆菌 FabH 的有效抑制剂。
