黄芩素的结构修饰以及抗肿瘤活性研究

为了改善黄芩素的抗肿瘤活性。本实验以黄芩素为原料,对其进行结构修饰。首先通过mannich反应,在8位引入胺亚甲基,然后通过酰基化反应在7位(6位)酚羟基上引入不同的疏水性基团。并利用CCK-8法对目标化合物进行抗MCF-7肿瘤细胞的活性评价。结果合成得到了6个目标化合物,通过1HNMR、13CNMR、MS和化学手段相结合的方法确定了其结构,其中化合物2~6为新化合物。实验利用黄酮类邻二酚羟基的特性,通过与氯化锶的络合反应,巧妙而简单的确证了所得目标化合物的酯键是在化合物的7位羟基上。抗MCF-7肿瘤活性实验表明,在黄芩素8位上引入含氮原子的胺亚甲基后活性比先导化合物黄芩素强,在其7位上再引入酯键后3个化合物活性比先导化合物强。

Structural modification and antitumor activity of baicalein

In order to improve the anti-tumor activity of baicalein,it was structurally modified.First,an amine methylene group is introduced to the 8-position by a mannich reaction,and then a different hydrophobic group is introduced to the 7-position (6-position) phenolic hydroxyl group by an acylation reaction.The target compound was evaluated for activity against MCF-7 tumor cells by the CCK-8 method.As a result,six target compounds were synthesized,and compound 2-6 are new compounds.Their structures were determined by a combination of 1H NMR, 13 C NMR,MS and chemical methods.The chemical methods utilized the characteristics of the o -diphenol hydroxyl group of flavonoid,which could react with ruthenium chloride to confirm that the ester bond of the compounds was at the 7-position hydroxyl group.Activity experiments showed that the activity of the compound with an amine-methylene group that containing a nitrogen atom at the 8-position is stronger than the lead compound.And after the ester bond is introduced at the 7-position,the activity of most compounds becomes better.