雄甾-3β,5α,6β-三醇衍生物的合成与抗癌活性

Synthesis and anticancer activity of androst-3β,5α,6β-triol derivatives

目的:合成3β,5α,6β-三羟基雄甾-17β-衍生物并考察其体外抗癌活性,探讨17β-侧链对抗癌活性的影响。方法:以孕烯醇酮为原料经乙酰化、溴仿反应、甲酯化、过氧化氢氧化、水解、再分别进行乙酯化和丁酯化等步骤合成了4个目标化合物;以孕烯醇酮、醋酸去氢表雄酮和薯蓣皂素为原料经过氧化氢氧化等步骤合成了3个目标化合物;3β,5α,6β-三羟基孕甾-20-酮经格式反应等步骤合成2个目标化合物。采用MTT活细胞染色法,对目标化合物进行BEL-7402人肝癌细胞体外增殖抑制实验。结果:合成了9个目标化合物并经元素分析、IR和~1HNMR确证了结构。结论:L7,L11和L12对BEL-7402人肝癌细胞有一定的抗癌活性,L12抗癌活性最好。

Objective： To synthesize androst-3β,5α,6β-triol-17β-derivatives and investigate their anticancer activities and impact of their 17β-side chain on the activities. Methods： Four target compounds were synthesized from pregnenolone as raw material via acetylation,bromoform reaction,methyl esterification,hydrogen peroxide oxidation,hydrolysis,and then ethylesterification and butyl esterification,respectively; 3 target compounds from pregnenolone,prasterone acetate and diosgenin via hydrogen peroxide oxidation etc.; and other 2 target compounds from 3β,5α,6β-trihydroxypregn-20-one via Grignard reaction etc. The proliferation-inhibiting activities of the 9target compounds were tested in human hepatocellular carcinoma BEL-7402 cell line by MTT live cell staining.Results： The 9 compounds were synthesized and corroborated structurally via elemental analysis,IR and-1 HNMR.Conclusion： L7,L11 and L12 have certain anticancer activities,and L12 is the best.