水飞蓟宾衍生物的设计合成及抗肿瘤活性研究  

Synthesis and antitumor activity of silybin derivatives

作　　者：赵风菊 霍荣迪 刘家越 李学城 孟艳秋 ZHAO Feng-ju;HUO Rong-di;LIU Jia-yue;LI Xue-cheng;MENG Yan-qiu(College of Pharmaceutical and Bioengineering,Shenyang University of Chemical Technology,Shenyang 110142,China)

机构地区：[1]沈阳化工大学制药与生物工程学院,辽宁沈阳110142

出　　处：《中国药物化学杂志》2023年第6期415-423,共9页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金项目(21372156);辽宁省重点研发计划项目(2019JH2/10300034);辽宁省教育厅重点项目(LJKZ0427);辽宁省教育厅面上项目(LJKZ0427);沈阳化工大学重点攻关和服务地方项目(LDB2019001)。

摘　　要：目的设计合成一系列新型水飞蓟宾衍生物,进行生物活性测试及分子对接研究。方法以天然产物水飞蓟宾为先导化合物,对其C-23位羟基进行结构修饰,设计合成新型水飞蓟宾衍生物;采用MTT法,用人肺癌细胞(A549)和乳腺癌细胞(MCF-7)进行初步体外抗肿瘤筛选;利用计算机辅助药物设计方法分析所合成化合物关键基团与靶蛋白的作用方式。结果合成了12个未见文献报道的水飞蓟宾衍生物,结构均经^(1)H-NMR、^(13)C-NMR及MS谱确证。活性测试结果表明,化合物Ⅰ_(3)、Ⅰ_(5)对肿瘤细胞的抑制活性与阳性对照药alpelisib相当。结论经过结构修饰后的水飞蓟宾衍生物具有一定的抗肿瘤作用,值得进一步研究。A series of new silybin derivatives were designed and synthesized for biological activity test and molecular docking study.Twelve new silybin derivatives were synthesized by modifying the C-23 hydroxyl group of natural product silybin and their structures were confirmed by^(1)H-NMR,^(13)C-NMR and MS.Breast cancer cells(MCF-7)and human lung cancer cells(A549)were used for preliminary anti-tumor activity screening in vitro by MTT assay.The activity test showed that the target compoundsⅠ_(3)andⅠ_(5)were equivalent to the positive control drug alpelisib.The structurally modified silybin derivatives have certain anti-tumor effects and deserve further study.

关 键 词：水飞蓟宾衍生物 分子对接 结构修饰 抗肿瘤 

分 类 号：R914[医药卫生—药物化学]