靶向Aβ聚集体的嘧啶及吡啶荧光探针的生物学评价
Evaluation of pyrimidine and pyridine based fluorescent probes targeting β-amyloid aggregates
作者：姜倩;徐小平;程妍;
Author：
收稿日期： 年卷（期）页码：2019,34(03):-113-119
期刊名称：华西药学杂志
Journal Name：WEST CHINA JOURNAL OF PHARMACEUTICAL SCIENCES
关键字：阿尔茨海默病;荧光成像;分子探针;Aβ聚集体;Aβ斑块;嘧啶;吡啶;APP/PS1
Key words：
基金项目：国家自然科学基金资助项目(批准号:81402891)
中文摘要
目的设计并制备具有嘧啶或吡啶结构的荧光探针,并评价探针的光学性能、与Aβ_(1-42)聚集体的亲和力以及入脑行为。方法以2-甲基吡啶或4-甲基嘧啶为起始原料,通过缩合反应合成了化合物Ⅰ～Ⅲ,并通过~1HNMR、~(13)CNMR与HRMS确认结构。考察所制备探针与Aβ_(1-42)聚集体混合前后的光学变化;通过体外饱和试验考察其与Aβ_(1-42)聚集体的亲和力;通过APP/PS1鼠脑切片的体外荧光染色考察探针与脑内Aβ斑块的特异结合;通过离体脑成像试验考察化合物Ⅲ在脑部的摄取与清除过程。结果该系列化合物与Aβ_(1-42)聚集体混合后均显示荧光增强,且具有良好的亲和力,并均能够特异性标记APP/PS1转基因小鼠脑切片上的Aβ斑块;其中,化合物Ⅲ能够有效透过血脑屏障,并具有良好的脑内代谢能力。结论该系列化合物可用于特异性荧光标记Aβ_(1-42)聚集体,且进一步修饰嘧啶结构,将有望得到新型脑内Aβ斑块靶向的荧光显像剂。
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