3-取代-B-降胆甾醇-6-(N-甲基)缩氨硫腙衍生物的合成及抗肿瘤活性评估  

Synthesis and in vitro antiproliferative activity evaluation of 3-substituted-b-norcholesteryl-6-(N-methyl)thiosemicarbazone derivatives

作　　者：甘春芳 庞婷婷 庞春玲 崔建国 彭子宁 黄燕敏 GAN Chun-fang;PANG Ting-ting;PANG Chun-ling;CUI Jian-guo;PENG Zi-ning;HUANG Yan-ming(Guangxi Key Laboratory of Natural Polymer Chemistry and Physics,College of Chemistry and Material Science,Nanning Normal University,Nanning 530001,China)

机构地区：[1]广西天然高分子材料与物理重点实验室,南宁师范大学化学与材料科学学院,广西南宁530001

出　　处：《化学研究与应用》2020年第8期1449-1460,共12页Chemical Research and Application

基　　金：国家自然科学基金项目(21762008,21562007)资助;广西自然科学基金项目(2018GXNSFAA281245)资助;广西八桂学者团队项目资助。

摘　　要：从胆甾醇出发,经过4步反应,合成了系列不同的3-取代-B-降胆甾醇-6-(4′-甲基)缩氨硫腙衍生物,采用IR、NMR及HRMS对合成物进行了结构表征。同时,分别采用人乳腺癌细胞(MCF-7)、人卵巢癌细胞(SKOV3)、人乳腺导管癌细胞(T47D)及人正常肾上皮细胞(HEK293T),研究了目标产物对这些细胞的抑制生长增殖活性。结果表明,除了乙酯基取代化合物外,当底物中3-羟基改变成为其它酯取代基或含氮的肟基及肟醚官能团后,原底物的细胞毒性显著降低。然而,3-乙酯基的存在对底物的抑制肿瘤细胞生长增殖活性没有明显影响,却大大降低化合物对人正常肾上皮细胞(HEK293T)的抑制生长增殖活性。Starting from cholesterol,a series of different 3-substituted-B-nor-cholesterol-6-(4′-methyl)thiosemicarbazone derivatives were synthesized in 4 steps and their chemical structures were characterized by IR,NMR and HRMS.At the same time,the antiproliferative activity of the target products against human breast cancer cells(MCF-7),human ovarian cancer cells(SKOV3),human breast ductal carcinoma cells(T47D)and human normal renal epithelial cells(HEK293T)were investigated.The results showed that the cytotoxicity of the substrates was significantly reduced when the 3-hydroxyl group was converted into other ester groups,oxime or oxime ether groups,except for the ethyl ester substituent.However,the presence of 3-ethyl esters had no significant effect on the antiproliferative activity of the substrate against the tumor cells,but greatly reduced the inhibition activity of the compound on human normal renal epithelial cells(HEK293T).

关 键 词：胆甾醇 B-降胆甾醇 B-降胆甾醇-6-(4′-甲基)缩氨基硫脲衍生物 抗肿瘤活性 3-甾体羧酸酯 

分 类 号：O629.29[理学—有机化学]