State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
Eur J Med Chem. 2010 Sep;45(9):4358-64. doi: 10.1016/j.ejmech.2010.05.033. Epub 2010 May 24.
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.
二十种新的席夫碱通过 5-氟-水杨醛和伯胺反应合成，作为 FabH 的有效抑制剂。这些化合物被检测对大肠杆菌、荧光假单胞菌、枯草芽孢杆菌和金黄色葡萄球菌的抗菌活性。具有强抗菌活性的化合物被测试其对大肠杆菌 FabH 的抑制活性。（E）-4-氟-2-((4-羟基苯乙基亚氨基)甲基)苯酚（10）表现出最强的抗菌活性，MIC 为 1.56-6.25μg/mL，对测试的细菌菌株具有最强的 FabH 抑制活性，IC50 为 2.7μM。进行对接模拟以将化合物 10 定位到大肠杆菌 FabH 的活性部位，以确定可能的结合构象。
