Study of acylhydrazone derivatives with deoxygenated seven-membered rings as potential β-ketoacyl-acyl carrier protein synthase Ⅲ(FabH)inhibitors
Fatty actci biosynthesis is essential for bacterial survival.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 highly conserved among Gram-positive and Gram-negative bacteria.Following previous studies,a series of acylhydrazone derivatives with deoxygenated rings were synthesized in this work.For all of the 36 analogues synthesized,studies using H NMR,C NMR,MS and elemental analyses were conducted.Their biological activities were also evaluated against two Gram-negative bacterial strains:E.coli and P.aeruginosa,and two Gram-positive bacterial strains: B.subtilis and S.aureus by the MTT method as potential FabH inhibitors.The resulting compound F18 showed the highest antibacterial activity with MIC values of 1.56-3.13 μg mL-1 against the tested bacterial strains and was found to be the most potent E.coli FabH inhibitor with an IC50 value of 2.0 μM.Molecular modeling simulation studies were performed in order to predict the biological activities of compound F18 into the E.coli FabH active site.
Yang Zhou Yin Luo Yu-Shun Yang Liang Lu Hai-Liang Zhu
State Key Laboratory of Pharmaceutical Biotechnology,Nanjing University,Nanjing 210023,People”s Republic of China
国内会议
大连
英文
752-759
2016-09-24（万方平台首次上网日期，不代表论文的发表时间）