甘草次酸C_3、C_(11)、C_(30)衍生物的合成及其体外抗肿瘤活性研究

Synthesis of glycyrrhetinic acid C_3,C_(11), and C_(30) derivatives and their antitumor activity in vitro

目的对甘草次酸C3、C11、C30进行结构改造及其体外抗肿瘤活性研究。方法甘草次酸经锌汞齐还原为11-脱氧甘草次酸,然后C30-羧基与卤代烃发生酯化反应,C3-羟基与甲基磺酰氯在0℃冰浴条件下发生甲基磺酰化反应,最后在104℃回流条件下与叠氮钠发生消除反应,从而得到目标产物;通过SRB法对上述合成的甘草次酸衍生物进行体外抗肿瘤活性研究。结果设计并合成了7个目标产物5a^5g,利用IR、MS和1H-NMR确证了结构;抗肿瘤活性筛选结果表明5a对MCF-7的抑制率比母体显著提高,5a、5c、5e对A549的抑制率均比母体有所提高。结论结构改造合理,对进一步开展甘草次酸衍生物的结构改造和抗肿瘤活性研究具有一定的参考价值。

Objective To modify the structures of glycyrrhetinic acid C3, Cll, and C3O and to study their antitumor activities in vitro. Methods Glycyrrhetinic acid was reduced to 11-deoxy-glycyrrhetinic acid by Zn-Hg. Then the carboxyl group at C30 reacted with halogenated hydrocarbons via esterification reaction, and the hydroxyl group at C3 reacted with methyl sufonyl chloride via methyl sulfonic acid reaction at 0 °C. The target product was obtained after the elimination reaction with sodium azide at 104 °C. The antitumor activities of the compounds were tested by SRB assay. Results Seven target products 5a-5g were synthesized, and were characterized by IR, MS and IH-NMR. The antitumor activity screening results showed that compound 5a exhibited higher inhibitory rate against MCF-7 cells than glycyrrhetinic acid, and compounds 5a--5g all exhibited higher inhibitory rates against A549 cells than glycyrrhetinic acid. Conclusion The structure modification ofglycyrrhetinic acid is reasonable, and provids some practical reference value for the further development on the structure modification of glycyrrhetinic acid derivatives and study on anti-tumor activity.