甘草次酸C3C11C30衍生物的合成及其体外抗肿瘤活性研究.PDF

• 6 • 现代药物与临床 Drugs Clinic 第 29 卷 第 1 期 2014 年 1 月 甘草次酸 C 、C 、C 衍生物的合成及其体外抗肿瘤活性研究 3 11 30 孟艳秋，杨 哲，张 萌，丁 一 沈阳化工大学 制药与生物工程学院，辽宁 沈阳 110142 摘 要：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 C -羧基与卤代烃发生酯化反应，C -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 30 3 ℃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 1 研究。结果 设计并合成了 7 个目标产物 5a～5g，利用 IR 、MS 和 H-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。 关键词：甘草次酸；11-脱氧甘草次酸；结构改造；抗肿瘤活性 中图分类号：R284.3 ；R287.2 文献标志码：A 文章编号：1674 - 5515(2014)01 - 0006 - 05 DOI: 10.7501/j.issn.1674-5515.2014.01.002 Synthesis of glycyrrhetinic acid C , C , and C derivatives and their antitumor 3 11 30 activity in vitro MENG Yan-qiu, YANG Zhe, ZHANG Meng, DING Yi College of Pharmaceutical and Biological Engineering, Shenyang University of Chemical Technology, Shenyang 110142, China Abstract: Objective To modify the structures of glycyrrhetinic acid C3, C11, and C30 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 ℃. The target product was obtained after the elimination reaction with sodium azide at 104 ℃. 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 1H-NMR. The antitumor activ