孕烯醇酮肟衍生物的合成与体外抗癌活性

Synthesis and in vitro Anticancer Activity of Derivatives of Pregnenolone-Oxime

研究孕烯醇酮肟衍生物的合成,并探讨其体外抗癌活性.以孕烯醇酮为原料,在甲酸中用质量分数为30%的过氧化氢溶液氧化、甲醇中碱水解得3β,5α,6β-三羟基孕甾-20-酮,3β,5α,6β-三羟基孕甾-20-酮、孕烯醇酮在乙醇中与盐酸羟胺经反应生成3β,5α,6β-三羟基孕甾-20-肟(收率43.3%,mp198.5~200.5℃)和3β-羟基孕甾-5-烯-20-肟(收率71.4%,mp 217.0~219.0℃).3β,5α,6β-三羟基孕甾-20-酮在乙酸中用乙酐酰化得3β,6β-二乙酰氧基-5α-羟基孕甾-20-酮,收率66.4%,mp 214~216℃.上述化合物经IR和~1HNMR确证了结构正确.采用MTT活细胞染色法,对目标化合物进行了BEL-7402人肝癌细胞体外增殖抑制实验.结果表明:上述3个目标化合物有一定的抗癌活性,但活性明显弱于胆甾-3β,5α,6β-三醇.胆甾-3β,5α,6β-三醇具有较好的抗癌活性.

To synthesize the derivatives of Pregnenolone-oxime and investigate their anticancer activities,3β,5α,6β-trihydroxy pregn-20-one was synthesized from Pregnenolone as rawmaterials through mass fractional 30 % H2O2 oxidation in formic acid. 3β,5α,6β-Trihydroxy pregn-20-oxime whose field was 43. 3 %,mp 198. 5 - 200. 5 ℃ and 3β-hydroxy pregn-5-en-20-oxime whose field was 71. 4 %,mp 217. 0- 219. 0 ℃,were synthesized respectively from 3β,5α,6β-trihydroxypregn-20-one and Pregnenolone,which reacted with NH2OH. 3β,6β-bis（ acetoxy）-5α-hydroxy pregn-20-one whose field was 66. 4 %,mp214 - 216 ℃,was synthesized from 3β,5α,6β-trihydroxy pregn-20-one by acetylation of（ Ac）2O in acetic acid. The compounds were corroborated structurally by IR and -1HNMR. The activities of the target compounds were tested on proliferation inhibition of human heptocellular carcinoma BEL-7402 cell line by MTT method. The anticancer activities of 3β,5α,6β-Trihydroxy pregn-20-oxime,3β-hydroxy pregn-5-en-20-oxime and 3β,6β-bis（ acetoxy）-5α-hydroxy pregn-20-one were much weaker than Cholesta-3β,5α,6β-triol. While cholesta-3β,5α,6β-triol was the better.