Novel anilinophthalimide derivatives as potential probes for beta-amyloid plaque in the brain.
Novel anilinophthalimide derivatives as potential probes for beta-amyloid plaque in the brain.
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DOI：
10.1016/j.bmc.2009.12.023
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发表时间：
2010-02
影响因子：
3.5
通讯作者：
Xin-hong Duan;J. Qiao;Yang Yang-Yang;M. Cui;Jiang-Ning Zhou;Boli Liu
中科院分区：
文献类型：
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作者：
Xin-hong Duan;J. Qiao;Yang Yang-Yang;M. Cui;Jiang-Ning Zhou;Boli Liu
本研究合成了一组新型的4，5-二苯胺基邻苯二甲酰亚胺衍生物，作为β-淀粉样蛋白（Aβ）斑块的探针。用代表性化合物9对来自阿尔茨海默病（AD）脑的海马组织切片进行染色，表明其选择性标记为Aβ斑块。放射性碘标记的[125 I]9与AD脑匀浆的结合亲和力为0.21 nM（Kd），除N-甲基-4，5-二苯胺邻苯二甲酰亚胺（Ki> 1000 nM）外，其他衍生物的结合亲和力范围为0.9 - 19.7 nM。[125 I]9具有最佳亲脂性（LogP值为2.16），其在正常小鼠体内的生物分布表现出良好的初始脑摄取（注射后2 min为5.16%ID/g）和快速的洗脱速率（60 min为0.56%ID/g）。令人鼓舞的结果表明，这种新的衍生物的[123 I]9可能有潜力作为一个在体内SPECT探针检测淀粉样蛋白斑块在大脑中。
A group of novel 4,5-dianilinophthalimide derivatives has been synthesized in this study for potential use as β-amyloid (Aβ) plaque probes. Staining of hippocampus tissue sections from Alzheimer’s disease (AD) brain with the representative compound 9 indicated selective labeling of it to Aβ plaques. The binding affinity of radioiodinated [125I]9 for AD brain homogenates was 0.21nM (Kd), and of other derivatives ranged from 0.9 to 19.7nM, except for N-methyl-4,5-dianilinophthalimide (Ki>1000nM). [125I]9 possessed the optimal lipophilicity with LogP value of 2.16, and its in vivo biodistribution in normal mice exhibited excellent initial brain uptake (5.16% ID/g at 2min after injection) and a fast washout rate (0.56% ID/g at 60min). The encouraging results suggest that this novel derivative of [123I]9 may have potential as an in vivo SPECT probe for detecting amyloid plaques in the brain.