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有机化学
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有机化学 ›› 2011, Vol. 31 ›› Issue (11): 1884-1892. 上一篇    下一篇

研究论文

具有肿瘤多药耐药逆转作用的金雀异黄素衍生物的合成及生物活性研究

芦金荣，邢辉，龙文艳，李运曼，杨煜，黄文龙*   

  1. (1中国药科大学有机化学教研室 南京 210009)
    (2中国药科大学新药研究中心 南京 210009)
    (3中国药科大学生理学教研室 南京 210009)
  • 收稿日期:2011-03-14 修回日期:2011-05-20 发布日期:2011-06-22
  • 通讯作者: 黄文龙（药科大学） E-mail:scieres3@cpu.edu.cn

Synthesis, Pharmacological Activity of A Series of Genistein Deriva-tives as Modulators of Multidrug Resistance

LU Jin-Rong, XING Hui, LONG Wen-Yan, LI Yun-Man, YANG Yu, HUANG Wen-Long   

  1. (1 Department of Organic Chemistry, China Pharmaceutical University, Nanjing 210009)
    (2 Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009)
    (3 Department of Physiology, China Pharmaceutical University, Nanjing 210009)
  • Received:2011-03-14 Revised:2011-05-20 Published:2011-06-22

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被引次数

21 | 1

细胞膜P-糖蛋白(P-gp)介导的药物外流是肿瘤多药耐药(MDR)产生的重要机制, 异黄酮类化合物可以通过抑制P-gp活性发挥MDR逆转作用. 通过对P-gp抑制剂进行结构分析, 以金雀异黄素为母体, 在其7位、8位及4位分别引进碱性边链, 设计、合成了20个金雀异黄素衍生物(其中16个未见文献报道), 并检测了其多药耐药逆转活性. 结果表明, 大多数目标化合物对人白血病耐药细胞株K562/A02具有不同程度的耐药逆转作用. 其中目标化合物8a, 8b, 8d, 8e逆转作用较强, 逆转倍数分别为8.97, 6.36, 5.19和5.82.

关键词: 异黄酮, 金雀异黄素, 多药耐药逆转活性, P-gp抑制剂, 合成

P-Glycoprotein (P-gp)-mediated drug efflux from cells is believed to be an important mechanism in multidrug resistance (MDR) in cancer chemotherapy. Isoflavone derivatives may selectively antagonize P-gp in MDR cancer cells. Twenty genistein derivatives containing a basic chain at 7-, 8- and 4-position were synthesized and evaluated for their MDR reversal activity in vitro. MTT assay showed that most of the target compounds exhibited MDR reversal activity on human chronic myeloid leukemia cell line K562/A02 in different levers and compounds 8a, 8b, 8d and 8e showed quite potent MDR reversal activity with the reversal fold (RF) values of 8.97, 6.36, 5.19 and 5.82.

Key words: isoflavones, genistein, multidrug resistance reversal activity, P-glycoprotein inhibitor, synthesis