7-二氟亚甲基-5-取代烷氧基黄酮类化合物的合成及其对人胃癌细胞增殖的抑制作用

Synthesis of 7 - Difluorinmethylene - 5 - substutited - alkoxyl Flavonid Compounds and Their Inhibitive Effects on Proliferation in Gastric Cancer Cells

目的设计和合成系列7-二氟亚甲基-5-取代烷氧基黄酮类化合物，观察其对人胃癌细胞增殖抑制作用。方法以白杨素（chrysin，5，7-二羟基黄酮，CbR）为先导化合物，先选择性地用二氟亚甲基取代ChR的7-羟基，合成化合物chR-1，再将一系列烷氧基取代chR-1的5-羟基，依次合成化合物ChR-2…chR-10。采用MTT比色法测定白杨素及白杨素衍生物对人胃癌SGC-7901细胞增殖抑制作用。结果合成10种7-二氟亚甲基-5-取代烷氧基黄酮类化合物，并分别进行波谱鉴定，其结构与设计相符；白杨素及白杨素衍生物对人胃癌细胞株SGC-7901具有不同程度的增殖抑制作用，其中ChR的IC50值为5．83μmoL，在ChR的C-7住引入二氟亚甲基合成的ChR-1的IC50值为3．98μmoL，表明其抑制人胃癌细胞增殖作用增强；进一步在ChR-1的C-5位引入烯丙氧基合成的ChR-10的IC50值为2．18μmoL，其IC50值为所有合成的7-二氟亚甲基-5-取代烷氧基黄酮类化合物中最低，表明其抑制SGC-7901细胞增殖作用最强。结论二氟亚甲基的C-7位取代获得白杨素衍生物的抑制人胃癌细胞增殖活性增强；在此基础上烯丙氧基的C-5住取代获得的7-二氟亚甲基-5-烯丙基白杨素具有更强的抑制人胃癌细胞增殖活性。

Objective To design and synthesize Chrysin （ChR）derivatives whose 7 -position hydroxyl substituted by difluorinmethylene and 5 - position hydroxyl substituted by a series of alkoxyls, then to investigate their inhibitive effects on the proliferation of gastric cancer cells. Methods Firstly , ChR was taken as lead compound, and its 7 - position hydroxyl was replaced selectively by difluurinmethy - lone, obtained ChR- 1, a chrysin derivative. Secondly, a series of alkoxyls were introduced into the 5 - position carbon of ChR- 1 respectively , then ChR- 2 to ChR- 10 were produced. MTT assay was used to test the proliferation inhibitive effects of Chrysin and the Chrysin derivatives on human gastric cancer cells. Results Judging from spectrum data we found the 10 kinds of the Chrysin derivatives were in accordance with our design; Both ChR and its derivatives had the inhibitive effects on the proliferation of gastric cancer eeUs in different degree, IC50 of ChR was 5.83 μmoL,IC50 of ChR- 1 was 3.98 μmoL, which indicated that the proliferation inhibition of ChR- 1 to human gastric canser Cell line was more effective than those of ChR, the lead compound. IC50 of ChR - 10 was 2.18μmoL, indicated it was the most effective in all synthesized chrysin derivatives. Conclusion Introduction of difluorinmethylene to 7 - position hydroxyl could enhance the inhibitive proliferation effects of Chrysin in human gastric cancer cells. On the basis of that, introduction of aUyl to 5- position hydroxl could greatly increase anticancer potency of Chrysin.