应用化学 ›› 2017, Vol. 34 ›› Issue (7): 789-794.DOI: 10.11944/j.issn.1000-0518.2017.07.160514

• 研究论文 • 上一篇    下一篇

汉防己甲素衍生物的合成及其生物活性

郭威凤a,许晋芳a,刘锐玲a,赵正保a*(),郭跃伟b   

  1. a山西医科大学药学院 太原 030001
    b中国科学院上海药物研究所 上海 201203
  • 收稿日期:2016-12-21 接受日期:2017-03-29 出版日期:2017-07-04 发布日期:2017-07-04
  • 通讯作者: 赵正保

Synthesis of Tetrandrine Derivatives and Their Biological Activity

GUO Weifenga,XU Jinfanga,LIU Ruilinga,ZHAO Zhengbaoa*(),GUO Yueweib   

  1. aSchool of Pharmaceutical Science,Shanxi Medical University,Taiyuan 030001,China
    bChinese Academy of Sciences,Shanghai Institute of Materia Medica,Shanghai 201203,China
  • Received:2016-12-21 Accepted:2017-03-29 Published:2017-07-04 Online:2017-07-04
  • Contact: ZHAO Zhengbao

摘要:

为寻找更为有效的抗肿瘤药物,改善汉防己甲素的抗肿瘤活性,本文以汉防己甲素为原料,经过Suzuki反应设计并合成了6个新的双苄基异喹啉类衍生物。 新化合物经过质谱(MS)、核磁共振氢谱(1H NMR)、核磁共振碳谱(13C NMR)等技术手段进行了结构确证。 采用细胞计数试剂盒(CCK-8)法初步评价了6个新化合物对人肺癌细胞(A549)和小鼠白血病细胞(P388)的抗肿瘤活性。结果表明,化合物均有不同程度的抗肿瘤活性,其中化合物H1、H4、H6对A549细胞的抗肿瘤活性(IC50<10 μmol/L)明显优于阳性对照汉防己甲素。

关键词: 汉防己甲素, Suzuki反应, CCK-8法, 抗肿瘤活性

Abstract:

In order to explore more effective anti-tumor drugs, and improve the anti-tumor activities of tetrandrine, six new bisbenzylisoquinoline derivatives of tetrandrine were designed and synthesized by Suzuki coupling. The structures of these compounds were confirmed by 1H nuclear magnetic resonance(1H NMR),13C nuclear magnetic resonance(13C NMR), and mass spectrometry(MS). Their inhibitory activities against human lung cancer cells(A549) and murine leukemia cells(P388) were evaluated by CCK-8(cell counting kit-8) method. All these compounds exhibit a certain level of anti-tumor activities, while compounds H1, H4, H6 possess better cytotoxicity profile than tetrandrine against A549 cells.

Key words: tetrandrine, Suzuki coupling reaction, cell counting kit-8 method, anti-tumor activity