新型金雀异黄素衍生物5-羟基-4’-硝基-7-取代酰氧基异黄酮的合成及抗肿瘤活性研究

Design and synthesis of genistein derivatives 5-hydroxy-4’-nitro-7-substituted-acyloxo-isoflavone and their antitumor effects

目的:对金雀异黄素进行结构改造,设计合成7 取代酰氧基5 羟基4’硝基金雀异黄素衍生物,并进行抗肿瘤活性测试。方法:以氯苄为起始原料,经取代、硝化、Friedel Crafts反应和环合,再与各种酰氯反应得到8 个目标化合物。结果:合成的目标化合物经元素分析和1HNMR确证其结构;其中化合物5B(5 羟基4’硝7 丙酰氧基异黄酮)体内外对人乳腺癌细胞株MDA MB 435均具有较强的抑制活性,IC50为0.017 mmol/L。结论: 金雀异黄素的4’引入硝基,同时7 位丙酰化产物具有良好的抗肿瘤活性。

Objective:To design and synthesize genistein derivatives 5-hydroxy -4’-nitro-7-sustituted-acyloxo-isoflavones and to evaluate their antitumor effects. Methods: Benzyl chloride was used as the raw material to obtain the title compounds by multi-step reaction: substitution, nitration, Friedel-Crafts reaction, cyclation reaction and acylation or alkylation. Results: Synthesized compounds were confirmed by 1HNMR and element analysis. Of them 5B(5-hydroxy-4’-nitro-7-propionyloxy isoflavone) had the most potent inhibitory effects on MDA-MB-435 breast cancer cells line in vitro and vivo. Conclusion: Propanoylation of 7-OH and substitution of OH by NO 2 can enhance the antitumor activity of genistein.