新型奥克梯隆型皂苷元荧光探针的设计、合成与活性评价

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

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.

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.