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目的在7-甲氧基或7-羟基苯并吡喃酮的3位引入各种取代苯基,以发现抗肿瘤活性更强的异黄酮类化合物。方法以丹皮酚和甲酸乙酯为原料,经多步反应制得关键中间体3-碘-7-甲氧基苯并吡喃酮(5),再经Suzuki coupling反应制得目标化合物,通过1H-NMR、MS和IR方法确定目标化合物的结构,部分化合物还进行了13C-NMR测定。选择人结肠癌细胞株HCT116和人肝癌细胞株7721为试验瘤株,以姜黄素和大豆异黄酮为阳性对照测定目标化合物的体外抗肿瘤活性。结果设计合成的20个新目标化合物均有一定的体外抗肿瘤活性,其中化合物6,9,16和19的活性较好,与对照品姜黄素的IC50值相当,明显优于对照品大豆异黄酮的IC50值。结论引入不同的3-取代苯基可以改变异黄酮类化合物的抗肿瘤活性;在这类化合物的3位苯基上引入甲基、甲氧基或三氟甲基体积较小的基团似乎有利于其抗肿瘤活性。
OBJECTIVE To introduce various substituted phenyl groups into the 3-position of 7-methoxy or 7-hydroxybenzopyrone to find isoflavones with more antitumor activity. Methods The key intermediate of 3-iodo-7-methoxybenzopyrone (5) was obtained from the reaction of paeonol and ethyl formate through multistep reaction. The target compound was obtained by Suzuki coupling reaction, 1H-NMR, MS and IR methods to determine the structure of the target compounds, some of the compounds were also 13 C-NMR determination. Human colon cancer cell line HCT116 and human hepatoma cell line 7721 were selected as test tumor strains. Curcumin and soy isoflavones were used as positive control to determine the in vitro antitumor activity of the target compounds. RESULTS: Twenty new target compounds were designed and synthesized to have certain in vitro antitumor activities. Among them, compounds 6, 9, 16 and 19 showed better activity than that of the reference substance curcumin, which was significantly better than the reference substance soy isoflavones IC50 value. Conclusion The introduction of different 3-substituted phenyl groups can change the antitumor activity of isoflavones; the introduction of methyl, methoxy or trifluoromethyl groups with smaller groups on the 3-position phenyl of these compounds seems to have Conducive to its anti-tumor activity.