高等学校化学学报 ›› 2019, Vol. 40 ›› Issue (10): 2097-2103.doi: 10.7503/cjcu20190246

• 有机化学 • 上一篇    下一篇

金诺芬衍生物的合成及抗肿瘤活性

张培全(),杨倩倩,龙惠丹,陈鑫   

  1. 广州医科大学蛋白质修饰与降解重点实验室, 广州 511436
  • 收稿日期:2019-04-26 出版日期:2019-09-05 发布日期:2019-09-05
  • 通讯作者: 张培全 E-mail:pqzhang@gzhmu.edu.cn
  • 基金资助:
    国家自然科学基金(No.81802405);广东省医学科研基金(No.A2018421);广东省中医药局基金项目(No.20192047)

Synthesis and Antitumor Activity of Auranofin Derivatives

ZHANG Peiquan(),YANG Qianqian,LONG Huidan,CHEN Xin   

  1. Key Lab of Protein Modification and Degradation, Guangzhou Medical University, Guangzhou 511436, China
  • Received:2019-04-26 Online:2019-09-05 Published:2019-09-05
  • Contact: ZHANG Peiquan E-mail:pqzhang@gzhmu.edu.cn
  • Supported by:
    † Supported by the National Natural Science Foundation of China(No.81802405);the Medical Scientific Research Foundation of Guangdong Province, China(No.A2018421);the Traditional Chinese Medicine Bureau of Guangdong Province, China.(No.20192047)

摘要:

设计合成了一类新型金诺芬衍生物, 采用核磁共振波谱(NMR)和高分辨质谱(HRMS)确认了其结构. 以目标化合物处理肿瘤细胞后, 采用四氮唑蓝盐(MTS)法检测细胞增殖情况, 用流式细胞仪检测细胞凋亡情况, 采用蛋白质免疫印迹(Western blot)法检测总的泛素化蛋白(Ub-Prs)、 K48 位链接多聚泛素化蛋白以及蛋白酶体外源性特异性底物(GFPu)的表达情况. 结果表明, 金诺芬衍生物可通过抑制蛋白酶体功能来发挥抗肿瘤效果.

关键词: 金诺芬衍生物, 蛋白酶体, 抗肿瘤活性

Abstract:

A new type of auranofin derivatives was synthesized and characterized by means of nuclear magne-tic resonance spectroscopy(NMR) and high resolution mass spectroscopy(HRMS). After treatment of tumor cells with target compounds, the effect of the target compound on cell viability was determined by MTS assay, apoptosis was detected by flow cytometry, Western blot was used to detect the effects of target compounds on total ubiquitinated protein(Ub-Prs), K48-linked polyubiquitinated protein and the expression of protease-specific substrate(GFPu) in vitro. The results showed that the auranofin derivative exerted a better antitumor effect by inhibiting the function of the proteasome.

Key words: Auranofin derivative, Proteasome, Antitumor activity

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