一些具有3-羟基-5-烯结构甾体骨架衍生物的合成及其VEGF抑制活性

 目的 设计合成一系列具有3-羟基-5-烯骨架的五环甾体骨架衍生物，并测试其抑制乳腺癌细胞新血管生成的活性。 方法 以孕烯醇酮醋酸酯为原料经3条不同合成路线对甾体D环16、17及20位进行一系列结构修饰。 结果 一共合成了12个化合物，其中新化合物有6个，结构均经核磁共振氢谱、碳谱及质谱确证。 结论 生物活性检测显示上述结构修饰的化合物对乳腺癌细胞血管内皮生长因子（Vascular Endothelial Growth Factor, VEGF）均有显著的抑制活性，EC50均在1 mmol/L或低于1 mmol/L的水平，其中化合物2a和4b的治疗指数TI值高于阳性对照品2-甲氧基雌二醇（2-Methoxyl Estradiol, 2-ME）

Synthesis and VEGF inhibition activities of some steroidal analogues with 3-hydroxy-5-ene moiety

Objective Some pentacyclic steroidal analogues with 3-hydroxy-5-ene moiety have been synthesized to evaluate inhibition of VEGF in breast cancer cells. Methods 16-Dehydropregnenolone acetate was used as starting material to proceed several modification on its D-ring via three different synthetic routes. Results Twelve target molecules,including 6 new molecules,have been synthesized.The structures of all target compounds were confirmed by 1H-NMR,13C-NMR and MS. Conclusions All target molecules showed potent in vitro inhibition of VEGF in breast cancer cells with EC50 values of 1 mmol/L or sub-mmol/L level.Among them TI values of compounds 2a and 4b were obviously larger than that of positive control 2-ME.