有机化学 ›› 2017, Vol. 37 ›› Issue (8): 2109-2114.DOI: 10.6023/cjoc201705039 上一篇    下一篇

研究简报

新型奥克梯隆型皂苷元荧光探针的设计、合成与活性评价

杨刚强, 杨延婷, 杨青, 李阳, 姜永涛, 傅风华, 王洪波   

  1. 烟台大学 新型制剂与生物技术药物研究山东省高校协同创新中心 分子药理和药物评价教育部重点实验室烟台 264005
  • 收稿日期:2017-05-27 修回日期:2017-05-27 出版日期:2017-08-25 发布日期:2017-07-18
  • 通讯作者: 杨刚强, 王洪波 E-mail:oceanygq@hotmail.com;hongbowangyt@gmail.com
  • 基金资助:

    国家自然科学基金(No.21502164)、山东省优秀中青年科学家科研奖励基金(No.BS2015YY039)、烟台大学博士科研基金(No.YX14B17)资助项目.

Novel Fluorescent Pyxinol-Based Probes: Design, Synthesis and Biological Evaluation

Yang Gangqiang, Yang Yanting, Yang Qing, Li Yang, Jiang Yongtao, Fu Fenghua, Wang Hongbo   

  1. Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, School of Pharmacy, Yantai University, Yantai 264005
  • Received:2017-05-27 Revised:2017-05-27 Online:2017-08-25 Published:2017-07-18
  • Contact: 10.6023/cjoc201705039 E-mail:oceanygq@hotmail.com;hongbowangyt@gmail.com
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No. 21502164), the Research Fund for Excellent Young and Middle-Age Scientists of Shandong Province (No. BS2015YY039), and the Startup Project of Doctor Scientific Research in Yantai University (No. YX14B17).

24R-奥克梯隆型皂苷元(Pyxinol),化学名称(20S,24R)-环氧达玛-3β,12β,25-三醇,是20(S)-原人参二醇的主要代谢产物,具有抗心肌缺血再灌注损伤(myocardial ischemia-reperfusion injury,MIRI)的活性.为了构建有活性的Pyxinol荧光探针,设计应用不同物理特性的连接臂连接Pyxinol与荧光基团异硫氰酸荧光素(FITC,常用荧光基团),以降低荧光大基团对Pyxinol的空间位阻干扰.合成的荧光探针用H9C2心肌细胞进行了体外抗MIRI活性评价.结果显示,具有亲水柔性乙氧基链的荧光探针保留了Pyxinol的抗MIRI活性.该活性小分子荧光探针的首次合成,为Pyxinol等人参皂苷的生物活性机制研究提供了重要的分子工具.

关键词: 人参皂苷, 荧光探针, 化学合成, 心肌缺血再灌注损伤

Pyxinol ((20S,24R)-epoxydammarane-3β,12β,25-diol), the 24R-ocotillol type sapogenin, shows the well protective activity against myocardial ischemia-reperfusion injury (MIRI) and is the main metabolite of 20(S)-protopanoxadiol. To build up the pyxinol fluorescent probes retaining the original biological activity, the linkers with different physical properties were designed to connect the fluorescein isothiocyanate (FITC, the common fluorescent dyes) to pyxinol to reduce the steric interference of bulky fluorescent group and pyxinol. The synthesized fluorescent probes were evaluated the in vitro anti-MIRI activity using H9C2 cardiac myocytes. The results showed that the molecular fluorescent probe with hydrophilic flexible polyethylene glycol (PEG) linker retained the anti-MIRI activity of pyxinol. The first synthesis of active molecular fluorescent probe will provide the key molecular tool for studying biological activity mechanism of pyxinol and other ginsenosides.

Key words: ginsenoside, fluorescent probe, chemical synthesis, myocardial ischemia-reperfusion injury