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.
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 IC50 value 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).
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