羟基胆烷酸类衍生物的抗癌活性研究Ⅱ.3β,5α,6β三羟基胆甾烷-24酸-及3β,6β-二羟基胆甾-4-烯-24-酸衍生物的合成及其抗癌活性

Study on the antitumor activity of hydroxycholanic acid derivatives Synthesis and in vitro antitumor activity of 3β ,5α ,6-trihydroxycholanic acid derivatives and 3β ,6β-dihydroxychol-4-enic acid derivatives

目的探讨侧链极性的改变对氧代固醇类化合物抗癌活性的影响。方法以去氧猪胆酸为起始原料合成共 2 2个 (其中 14个未见文献报道 )侧链具一定极性、母环结构为 3β ,5α ,6 β 三羟基及 3β ,6 β 二羟基 Δ4 烯胆甾 2 4 酸衍生物 ,并以 3β ,5α ,6 β 三羟基胆甾烷 (10 )和 3β ,6 β 二羟基胆甾 4 烯 (11)为对照 ,比较其体外抗癌活性。结果与结论少部分化合物的抗癌活性比对照物稍强 ,大部分基本持平 ,少部分活性消失。希望从 3β ,5α ,6 β 三羟基及 3β ,6 β 二羟基 Δ4 烯胆甾 2 4 酸衍生物中找到比现有的氧代固醇抗癌活性更强的化合物的设想 ,目前尚未达到预期目的。

Aim To investigate whether the changing of the side chain of polarity may alter the antitumor effect of the oxysterols.Method Starting from hyodesoxycholic acid,22 compounds were synthesized(among them,14 were new ones).Ring A and B of these compounds bear the structural features of 3 β ,5 α ,6 β trihydroxy or 3 β ,6 β dihydroxy Δ 4 ene and their side chains all possess a varied degree of polarity.Compared with 3 β ,5 α ,6 β thihydroxycholestane(10)and 3 β ,6 β dihydroxycholest 4 ene(11)respectively, in vitro antitumor activities of these 22 compounds were tested with murine L 1210 leukemia cell line.Result and conclusion For most of the compounds tested,no evident change on antitumor effect had been observed,although a few had slightly stronger effect and some of them lost their activity.Therefore,the goal to obtain antitumor oxysterols with stronger activity has not yet been achieved through synthesizing cholanic acid derivatives with sturctural features of 3 β ,5 α ,6 β triol and/or 4 ene 3 β ,6 β diol.