17-肟基雄甾烷类化合物的合成及抗肿瘤活性研究

Synthesis and antiproliferative activities of 17-hydroximinosubstituted androstane compounds

目的设计合成一系列17-肟基雄甾烷类化合物,并进行体外抗肿瘤活性测试。方法以去氢表雄酮为起始原料,通过PCC氧化、选择性还原以及选择性肟化,合成一系列17-肟基雄甾烷类化合物;采用MTT法对合成的化合物进行体外抑制肿瘤细胞增殖活性测试。结果与结论设计合成了5个17-肟基取代雄甾烷类化合物,活性研究表明,这5个化合物对人鼻咽癌CNE细胞株和人胃癌SGC-7901细胞株表现出弱的抑制活性。

In recent years, a lot of steroidal compounds with different structural characteristics, such as polyhydroxyl sterols, steroidal glucosides, steroidal oximes and sodium sterol sulfates, were isolated from marine organisms. Many of them have novel structures and biological activities against the tumor, virus and bacteria. Therefore,it has attracted organic chemists and medicine scientists strong interest. In this paper, using dehydroepiandrosterone as starting material, via PCC oxidation, selective reduction and selective oximation, five hydroximino-substituted androstane compounds were obtained. （17E）-androst-4-en-3, 6-dione-17-oxime （3）, （ 3E,6E, 17E） -androst-4-en-3,6,17-trioxime （ 4 ）, （17E） -androst-3,6-dione-17-oxime （ 7 ）, （ 3E, 6E, 17 E） -androst-3,6,17-trioxime （ 8 ） and （ 6E, 17 E） -3-hydroxyl-androst-4-en-6,17-dioxime （9）. Their antiproliferative activities against CNE and SGC-7901 cells were assayed in vitro. The results show that all compounds show weak cytotoxic activity against SGC-7901 cells with IC50 values 145.9,75.3,44. 1,100. 8 and 117.4 μmol.L^-1. Compounds 3,4,8 and 9 show weak cytotoxic activity against CNE cells with IC50 values 66.6,141.9,63.4 and 51.2 μmol.L^-1 ,respectively.