靶向CDK4/6抑制剂水飞蓟宾衍生物的合成及抗肿瘤活性研究  

Study on the modification and anti-tumor activity of silybin derivatives for CDK4/6 targeted

作　　者：高诗特 蒯振彧 张志鹏 孟艳秋[1] GAO Shi-te;KUAI Zhen-yu;ZHANG Zhi-peng;MENG Yan-qiu(Shenyang University of Chemical Technology,Shenyang 110142,China;Shenyang Institute of Science and Technology,Shenyang 110166,China;Ma'anshan Vocational and Technical College,Ma'anshan 243031,China)

机构地区：[1]沈阳化工大学,辽宁沈阳110142 [2]沈阳科技学院,辽宁沈阳110166 [3]马鞍山职业技术学院,安徽马鞍山243031

出　　处：《药学学报》2023年第3期721-728,共8页Acta Pharmaceutica Sinica

基　　金：辽宁省重点研发计划项目(2019JH2/10300034);辽宁省教育厅重点项目(LJKZ0427);沈阳市重大科技成果转化项目(20-203-5-45);沈阳化工大学重点攻关项目(LDB2019001);安徽省高校自然科学研究项目(KJ2021A1340)。

摘　　要：本文借助计算机辅助设计,结合已上市的CDK4/6抑制剂活性片段构建药效团模型,设计合成了15个水飞蓟宾C-7位结构衍生物。经MS、^(13)C NMR和^(1)H NMR谱图解析确认,15个化合物均为未见文献报道的新化合物。采用MTT法,对人肝癌细胞(HepG-2)进行了初步的体外抗肿瘤活性研究。实验结果表明,所有化合物均比母体水飞蓟宾的活性有提高,其中化合物I_(1)对人HepG-2细胞有一定的抑制作用,值得进一步研究。By using computer-aided drug design,the activities group model which CDK4/6 inhibitors on the market were introduced to silybin C-7,and a series of silybin derivatives were designed and synthesized,and the structure was confirmed by MS,^(13)C NMR and ^(1)H NMR.The in vitro antitumor activity evaluation of the target compound was carried out by MTT method,and the in vitro anti-tumor activity was carried out in human hepatocellular carcinoma cells(HepG-2).Experimental results show that all compounds are higher than the activity of the parent silybin,of which compound I1has a certain inhibitory effect on human HepG-2 cells,which is worth further study.

关 键 词：水飞蓟宾衍生物 CDK4/6抑制剂 结构修饰 抗肿瘤活性 

分 类 号：R914[医药卫生—药物化学]