3-(4-羟基苯基)-6-甲氧基-7-羟基-4H-色烯-4-酮的合成及其抑制新生血管的作用

 目的 合成目标化合物3-(4-羟基苯基)-6-甲氧基-7-羟基-4H-色烯-4-酮(化合物1)，考查该化合物抑制新生血管生长活性。 方法 以异香兰素为起始原料，经过插氧、水解、酰化和环合四步反应合成目标化合物；以新生血管抑制剂2-甲氧基雌二醇为阳性对照，采用人脐静脉内皮细胞(human umbilical vein endothelial Cells, HUVECs)筛药模型和子宫内膜基质细胞(endometrial stromal cells, ESCs)模型分别测定该化合物的新生血管抑制活性和细胞毒性。结果 在合成路线上改进了文献方法，用常规反应替代了文献方法中较难控制的微波反应，同时提高了合成收率；生物活性测定结果显示目标化合物的EC50和TI值分别为47.37 μmol/L和7.39。 结论 首次报道了目标化合物抑制新生血管的作用，该化合物具有与2-甲氧基雌二醇相近的体外活性。

Synthesis and biological evaluation of 7-hydroxy-3- (4-hydroxyphenyl)-6- methoxy-4H-chromen-4-one as angiogenesis inhibitor

Objective To synthesize 7-hydroxy-3-(4-hydroxyphenyl)-6-methoxy-4H-chromen -4-one (Compound 1) and evaluate its anti-angiogenetic activity. Methods The title compound was synthesized via four steps involving oxidation, hydrolization, acylation and cyclization with isovanillin. The anti-angiogenetic activity and the cell toxicity of 1 were screened on human umbilical vein endothelial cells (HUVECs) and endometrial stromal cells (ESC) respectively with 2-methoxyestradiol as reference compound. Results An improved synthetic route to title compound was obtained, especially replacing the reported microwave reaction to cyclize the isoflavone core by the reaction under normal condition. The bioactivity assay data showed that the title compound exhibited potent anti-angiogenetic activity with EC50 as 47.37 μmol/L and TI as 7.39. Conclusions The title compound has the similar angiogenesis inhibitory activity to 2-methoxyestradiol.