新型肟基取代豆甾类化合物的合成及其抗肿瘤活性

以豆甾醇为原料,通过臭氧化将豆甾醇的C20—C22键断裂,再经过官能团转换,合成了22-肟基取代的单肟基化合物(3和9),6,22-二肟基取代的双肟基化合物(13和14)及3,6,22-三肟基化合物(17),其中涉及4个中间体(5~8)及目标化合物9,13,14和17共8个新化合物,其结构经~1H NMR,~(13)C NMR,IR和HR-MS(ESI)表征。采用MTT法测试了化合物对人胃癌细胞(SGC-7901)、人肝癌细胞(Bel-7404)和人体乳腺癌细胞株(He La)的体外抗肿瘤活性。结果表明,具有22-肟基取代的3-羟基-5-烯结构的豆甾化合物3对受试细胞均有一定活性,IC50分别为34±2μmol·L~(-1),32±1μmol·L~(-1)和38±3μmol·L~(-1)。但是进一步在甾核上引入肟基或羟基的其他几种类型化合物的抗肿瘤活性没有提高。

Synthesis and Antiproliferative Activities of Novel Stigmastane Compounds Substituted with Hydroximino Groups

A series of stigmastane compounds substituted with 22-hydroximino(3, 9), 6,22-dihydrox-imino(13, 14) and 3,6,22-trihydroximino(17) were synthesized through ozonation and functional group transformation methods using stigmasterol as starting material. Eight novel compounds including four intermediates(5~8) and target compounds(9, 13, 14 and 17) were involved. The structures were characterized by 1H NMR, 13C NMR, IR and HR-MS(ESI). The antiproliferative activities of compounds were evaluated against human gastric carcinoma ( SGC-7901 ) , human cervical carcinoma (HeLa) and human liver carcinoma(Bel-7404) cells. The results showed that compound 3 with 22-hydroximino and 3-hydroxy-5-enekey features displayed distinct antiproliferative activities to these cells with IC50 of 34 ± 2μmol·L-1 , 32 ± 1μmol·L-1 and 38 ± 3μmol·L-1 , respectively, and a further introduction of hydroximino or hydroxyl groupon steroidal nucleus did not enhance the antiproliferative activities of compounds.