State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
ChemMedChem. 2012 Sep;7(9):1587-93. doi: 10.1002/cmdc.201200225. Epub 2012 Jul 18.
Forty-three oxime derivatives were synthesized by allowing O-benzylhydroxylamines to react with primary benzaldehydes or salicylaldehydes; these products were gauged as potential inhibitors of β-ketoacyl-(acyl-carrier-protein) synthase III (FabH). Among the 43 compounds, 38 are reported herein for the first time. These compounds were assayed for antimicrobial activities against Escherichia coli, Pseudomonas aeruginosa, Pseudomonas fluorescens, Bacillus subtilis, Staphylococcus aureus, and Enterococcus faecalis. Compounds with prominent antibacterial activities were tested for their E. coli FabH inhibitory activities. 3-((2,4-Dichlorobenzyloxyimino)methyl)benzaldehyde O-2,4-dichlorobenzyl oxime (44) showed the best antibacterial activity, with minimum inhibitory concentrations of 3.13-6.25 μg mL(-1) against the tested bacterial strains, exhibiting the best E. coli FabH inhibitory activity, with an IC(50) value of 1.7 mM. Docking simulations were performed to position compound 44 into the E. coli FabH active site in order to determine the most probable binding conformation.
合成了 43 种肟衍生物，方法是使 O-苄基羟胺与一级苯甲醛或水杨醛反应；这些产物被评估为β-酮酰基-(酰基载体蛋白)合酶 III（FabH）的潜在抑制剂。在这 43 种化合物中，有 38 种是首次报道。这些化合物被检测对大肠杆菌、铜绿假单胞菌、荧光假单胞菌、枯草芽孢杆菌、金黄色葡萄球菌和粪肠球菌的抗菌活性。具有突出抗菌活性的化合物被测试对大肠杆菌 FabH 的抑制活性。3-((2,4-二氯苄氧基亚氨基)甲基)苯甲醛 O-2,4-二氯苄肟（44）表现出最好的抗菌活性，对测试的细菌菌株的最小抑菌浓度为 3.13-6.25μgmL(-1)，表现出最好的大肠杆菌 FabH 抑制活性，IC(50)值为 1.7mM。进行了对接模拟，将化合物 44 定位到大肠杆菌 FabH 的活性部位，以确定最可能的结合构象。
