N-(2-氨基苯基)-4-［N-(苯丙烯酰)氨基］苯甲酰胺的合成及体外抗肿瘤活性

doi:10.3969/j.issn.1000-1565.2018.02.005

河北大学学报(自然科学版) ›› 2018, Vol. 38 ›› Issue (2): 140-146.DOI: 10.3969/j.issn.1000-1565.2018.02.005

N-(2-氨基苯基)-4-［N-(苯丙烯酰)氨基］苯甲酰胺的合成及体外抗肿瘤活性

彭晓然,吴佳浓,付文涛,李胜辉,王书香

收稿日期:2017-12-25 出版日期:2018-03-25 发布日期:2018-03-25
通讯作者: 王书香(1965—),男,河北大城人,河北大学教授,主要从事抗肿瘤药物研究.E-mail:wsx@hbu.edu.cn
作者简介:彭晓然(1993—),女,河北藁城人,河北大学在读硕士研究生,主要从事抗肿瘤药物研究. E-mail:15720094539@163.com
基金资助:
河北省应用基础重点基金资助项目(15962602D);河北省自然科学基金资助项目(B2015201213)

Synthesis and in vitro antitumor activity of N-(2-aminophenyl)-4-cinnamamidobenzamide

PENG Xiaoran,WU Jianong,FU Wentao,LI Shenghui,WANG Shuxiang

Key Laboratory of Chemical Biology of Hebei Province, Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China

Received:2017-12-25 Online:2018-03-25 Published:2018-03-25

摘要/Abstract

摘要： 合成了系列苯甲酰胺(3a-3j)类组蛋白去乙酰化酶抑制剂(HDACi).采用MTT法检测了3a-3j对MCF-7、HeLa和A549细胞株的体外细胞毒性,采用荧光分析法测定了3a-3j对HDAC的抑制作用.结果表明:N-(2-氨基苯基)-4-{N-［(2-氯苯基)丙烯酰］氨基}苯甲酰胺(3b)和N-(2-氨基苯基)-4-{N-［(2-硝基苯基)丙烯酰］氨基}苯甲酰胺(3e)表现较高的活性,对HDAC的IC₅₀值分别为7.71和3.5 μmol/L,与西达苯胺(2.7 μmol/L)相当;3b对MCF-7、HeLa和A549细胞株的IC₅₀值分别为6.5、6.0和5.6 μmol/L,3e对MCF-7、HeLa和A549细胞株的IC₅₀值分别为3.9、3.1和2.9 μmol/L,与MS-275(3.5 μmol/L)相当.

关键词: N-(2-氨基苯基)-4-［N-(苯丙烯酰)氨基］苯甲酰胺, 组蛋白去乙酰化酶抑制剂, 细胞毒性

Abstract: A series of benzamide(3a-3j)histone deacetylase inhibitors(HDACi)were synthesized.Their activity for inhibiting histone deacetylase(HDAC)and in vitro cytotoxicity against MCF-7,HeLa,and A549 cell lines were determined by fluorescence analysis and MTT assay.The 2-substituted N-(2-aminophenyl)-4-cinnamamidobenzamides 3b and 3e exhibited high cytotoxicity and activity of inhibiting HDAC.The IC₅₀value of 3b and 3e for HDAC inhibition were 7.71 and 3.5 μmol/L,and closed to that of chidamide(2.7 μmol/L).The IC₅₀ value of 3b against MCF-7,HeLa,and A549 cell lines were 6.5,6.0,and 5.6 μmol/L;that of 3e against MCF-7,HeLa,and A549 cell lines were 3.9,3.1,and 2.9 μmol/L.The in vitro cytotoxicity of 3b and 3e is closed to that of MS-275(3.5 μmol/L).

Key words: N-(2-aminophenyl)-4-cinnamamidobenzamide, histone deacetylase inhibitor, cytotoxicity

中图分类号:

彭晓然,吴佳浓,付文涛,李胜辉,王书香. N-(2-氨基苯基)-4-［N-(苯丙烯酰)氨基］苯甲酰胺的合成及体外抗肿瘤活性[J]. 河北大学学报(自然科学版), 2018, 38(2): 140-146.

PENG Xiaoran,WU Jianong,FU Wentao,LI Shenghui,WANG Shuxiang. Synthesis and in vitro antitumor activity of N-(2-aminophenyl)-4-cinnamamidobenzamide[J]. Journal of Hebei University (Natural Science Edition), 2018, 38(2): 140-146.

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N-(2-氨基苯基)-4-［N-(苯丙烯酰)氨基］苯甲酰胺的合成及体外抗肿瘤活性

Synthesis and in vitro antitumor activity of N-(2-aminophenyl)-4-cinnamamidobenzamide

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