广东药学院学报2017，Vol.33Issue(2)：187-190,4.DOI:10.16809/j.cnki.2096-3653.2017021802
伏立诺他衍生物N2E的合成、鉴定及体外抗肿瘤活性研究
Study on synthesis and antitumor activity of vorinostat derivative N2E
摘要
Abstract
Objective To synthesize vorinostat derivative N2E and evaluate its anti-tumor activity.Methods Suberic acid was used as raw material to produce suberoyl anhydride by dehydration in the presence of acetic anhydride,then acetic anhydride ring opening and amidation with 2-ethoxy aniline in dichloromethane at 0 ℃,and eventually N2E was produced by esterification and aminolysis.The structure of N2E was identified by MS,1H NMR and 13C NMR.The inhibitory activity of N2E against lung cancer NCI-H1299,NCI-H460,A549 cells and glioma U251,MGR2 cell lines were investigated and the cytotoxicity to LO-2 cells was observed.Results The target compound was identified as vorinostat derivative N2E [N-(2-ethoxyphenyl)-N′-hydroxyoctanediamide],and the purity was about 99.1% by normalization method.The inhibitory effect of N2E on human lung cancer cells NCI-H1299,A549 and glioma cells U251,MGR2 were stronger than that of vorinostat (P<0.001),however the cytotoxicity of N2E on human normal liver cells LO-2 was weaker than that of vorinostat (P<0.001).Conclusion N2E was successfully synthesized by mixed anhydride method,and the inhibitory effect on NCI-H1299,A549,U251 and MGR2 were significant.关键词
伏立诺他衍生物/HDACi/抗肿瘤活性/混合酸酐法Key words
vorinostat derivative/HDACi/antitumor activity/mixed anhydride method分类
医药卫生引用本文复制引用
孙心愿,倪安然,王晓翔,冯冰虹..伏立诺他衍生物N2E的合成、鉴定及体外抗肿瘤活性研究[J].广东药学院学报,2017,33(2):187-190,4.基金项目
广东省科技计划项目(2013B021800079) （2013B021800079）
