These authors contributed equally to this work.
Novel Schiff-Base-Derived FabH Inhibitors with Dioxygenated Rings as Antibiotic Agents
Article first published online: 7 FEB 2013
Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Volume 8, Issue 3, pages 433–441, March 2013
How to Cite
Zhou, Y., Du, Q.-R., Sun, J., Li, J.-R., Fang, F., Li, D.-D., Qian, Y., Gong, H.-B., Zhao, J. and Zhu, H.-L. (2013), Novel Schiff-Base-Derived FabH Inhibitors with Dioxygenated Rings as Antibiotic Agents. ChemMedChem, 8: 433–441. doi: 10.1002/cmdc.201200587
- Issue published online: 22 FEB 2013
- Article first published online: 7 FEB 2013
- Manuscript Received: 25 DEC 2012
- National Natural Science Foundation of China. Grant Number: J1103512
- antibacterial agents;
- dioxygenated rings;
- β-ketoacyl-ACP synthase III
Fatty acid biosynthesis plays a vital role in bacterial survival and several key enzymes involved in this biosynthetic pathway have been identified as attractive targets for the development of new antibacterial agents. Of these promising targets, β-ketoacyl-acyl carrier protein (ACP) synthase III (FabH) is the most attractive target that could trigger the initiation of fatty acid biosynthesis and is highly conserved among Gram-positive and -negative bacteria. Designing small molecules with FabH inhibitory activity displays great significance for developing antibiotic agents, which should be highly selective, nontoxic and broad-spectrum. In this manuscript, a series of novel Schiff base compounds were designed and synthesized, and their biological activities were evaluated as potential inhibitors. Among these 21 new compounds, (E)-N-((3,4-dihydro-2H-benzo[b][1,4]dioxepin-7-yl)methylene)hexadecan-1-amine (10) showed the most potent antibacterial activity with a MIC value of 3.89–7.81 μM−1 against the tested bacterial strains and exhibited the most potent E. coli FabH inhibitory activity with an IC50 value of 1.6 μM. Docking simulation was performed to position compound 10 into the E. coli FabH active site to determine the probable binding conformation.