白杨素抗肿瘤衍生物的合成及其构效关系

目的合成一系列白杨素衍生物并结合体外实验探讨白杨素衍生物抗肿瘤作用的构效关系。方法以5,7-二羟基黄酮为原料,通过取代、水解、酰胺缩合等化学反应引入一些极性不同的小分子化合物,合成一系列白杨素的衍生物,然后采用MTT比色法检测白杨素及其衍生物对食管癌EC109细胞、肝癌HepG2细胞、宫颈癌Hela细胞的增殖抑制作用。结果化合物Ⅲa、Ⅲb、Ⅲc、Ⅲd、Ⅲf对抑制EC109增殖表现出的抗癌活性较白杨素有明显的提高,化合物Ⅲa、Ⅲd、Ⅲe、Ⅲf对抑制HepG2增殖表现出的抗癌活性较白杨素有明显的提高,其中Ⅲd和Ⅲf的抗肿瘤作用显著;白杨素及其衍生物对抑制Hela细胞的增殖均较高,但其衍生物抗肿瘤作用与白杨素相比没有提高。结论引入极性基团对白杨素的抗肿瘤活性有明显的提高,经过极性基团修饰后的白杨素衍生物能明显提高对EC109、HepG2细胞增殖抑制作用。

Synthesis of chrysin derivatives as anti-Tumor agents and relationship of their structure-activity

Objective A series of chrysin derivates was synthesized and their anti-tumor activity was evaluated to study the structure-activity relationship of chrysin derivates.Methods To synthesize a series derivates from 5,7-dihydroxyflavone by leading some small molecules with different polarities,used the chemical methods of substitution reaction,hydrolysis,amide condensation reaction,and then evaluate for their anti-proliferative activities against human cancer cell EC109,HepG2,Hela by MTT assay.Results The anti-tumor activities of Ⅲa,Ⅲb,Ⅲc,Ⅲd,Ⅲf against EC109 were better than chrysin,and the inhibitory of Ⅲa,Ⅲc,Ⅲd,Ⅲe,Ⅲf against HepG2 increased compared with chrysin,but their anti-tumor activities against Hela had no deference.Conclusion Anti-tumor effect of chrysin derivates is positively correlated with polarity of these small molecules,and chrysin derivates with high polarity display better anti-tumor activities against EC109 and HepG2 in vitro.