白藜芦醇类似物的合成及雌激素样活性研究

目的设计合成白藜芦醇的类似物,进行体外雌激素样活性评价。方法取代溴苄经磷酰化、缩合、脱甲基制得目标分子(1-9),并用人乳腺癌细胞增殖试验测定其体外雌激素样活性。结果目标化合物经核磁共振等确证其结构;白藜芦醇类似物具有不同程度的雌激素样活性,其中以4,4'-二羟基二苯乙烯(2)最高。相对增殖率结果提示:白藜芦醇、2和4为雌激素受体的全激动剂,3,7,8和9为雌激素受体的部分激动剂,1,5和6为雌激素受体的弱激动剂。结论首次报道白藜芦醇类似物的体外雌激素样活性,有进一步研发的价值。

Synthesis and estrogen-like activity of resveratrol analogues

OBJECTIVE To synthesize resveratrol analogues,and evaluate their estrogen-like activity in vitro.METHODS The target compounds(1-9) were prepared from substituted benzyl bromide via phosphorylation,condensatiom and demethylation,then their estrogen-like activities on sensitive human mammary cancer(MCF-7) cell were determined by MTT assay. RESULTS All target compounds were confirmed by mp and 1HNMR. All resveratrol analogues had different estrogenic activity.The results of relative proliferative effect(RPE) suggested that resveratrol,2,4 were full-agonists of estrogen receptor;3,7,8,9 were partial-agonists of estrogen receptor,1,5,6 were weakly-agonists of estrogen receptor.Of the total,2 showed the strongest effect in promoting MCF-7 cell growth.CONCLUSION It was the first report that resveratrol analogues had estrogen-like activity and they could be a new source of estrogenic agent.