6,7,4′-三羟基异黄酮(T2)水溶性衍生物的合成及其对宫颈癌细胞抑制作用的研究

Synthesize of water-solubility derivant of 6,7,4′-trihydroxyisoflavone(T2) and study of its inhibition effect on human breast cancer cell proliferation

目的合成6,7,4′-三羟基异黄酮(6,7,4′-trihydroxyisoflavone,T2)水溶性衍生物,对其结构进行表征,并对其抗肿瘤活性进行评价。方法通过磺化反应在原料B环中3'位引入磺酸基(-SO3H),进一步浓氨水氨化后得到水溶性显著提高的异黄酮衍生物,通过氢谱、碳谱、质谱、元素分析等对其结构进行表征,CCK-8法及流式测定其杀伤宫颈癌细胞(Hela)的活性。结果通过上述方法得到两种水溶性异黄酮衍生物T2-SO3H·2H2O和T2-SO3(NH4)2,产率分别为:96%、75%,生物试验显示其中T2-SO3(NH4)2抗肿瘤活性显著增强。结论与T2相比,其水溶性衍生物具有更高的生物相容性及抗肿瘤活性,有广泛的生物应用前景。

Objective To synthesize of water-solubility derivant of 6,7,4＇- trihydroxyisoflavone （T2）, to characterize its structure and to evaluate its anti-tumor activity. Methods The sulfonic group（-SO3 H） was grafted to 3＇position in loop B of T2 through sulfonation reaction,then strong aqua was added to above production, and obtained a water-solubility elevated compound named T2-SO3 （NH4）2 through ammoniation. The construction of T2-SO3 （NH4）2 was characterized by ^1H-NMR,^13C NMR, MS and element analysis. Its activity for killing human breast cancer cells （Hela） was analyzed by CCK-8 assay and flow cytometry. Results The two kinds of water-solubility derivant of T2-SO3H · 2H2O and T2-SO3（NH4）2 were obtained through above methods, and their yield rates were 96 % and 75% respectively. The biological experiments showed that the anti-tumor activity of T2-SO3 （NH4）2 was significantly enhanced. Conclusion Compared to T2,T2-SO3 （NH4）2 exhibit higher bioeompatibility and anti-tumor activity with vast biological application prospect.