Synthesis and biological evaluation of novel styryl benzimidazole derivatives as probes for imaging of neurofibrillary tangles in Alzheimer's disease
Synthesis and biological evaluation of novel styryl benzimidazole derivatives as probes for imaging of neurofibrillary tangles in Alzheimer's disease
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DOI：
10.1016/j.bmc.2013.02.054
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发表时间：
2013-06-01
影响因子：
3.5
通讯作者：
Saji, Hideo
中科院分区：
文献类型：
--
作者：
Matsumura, Kenji;Ono, Masahiro;Saji, Hideo
本文介绍了苯乙烯基苯并咪唑（SBIM）衍生物作为阿尔茨海默病（AD）患者神经元缠结（NFT）成像剂的合成和生物学评价。以4-碘苯-1，2-二胺和取代肉桂醛为原料合成了SBIM衍生物。在使用重组tau和A β（1-42）聚集体的结合实验中，SBIM-3对tau聚集体显示出比Ab 1 -42聚集体更高的亲和力（K-d值的比率为2.73）。在体外放射自显影和荧光染色中，[I-125]SBIM-3（或SBIM-3）结合AD脑组织切片中的NFT。在使用正常小鼠的生物分布实验中，所有[I-125]SBIM衍生物均显示出高的脑初始摄取（注射后2 min为3.20-4.11%ID/g）和快速清除（注射后60 min为0.12-0.33%ID/g）。总之，适当的结构修饰的SBIM衍生物可能会导致更有用的代理在AD脑NFT的体内成像。(C)2013爱思唯尔有限公司保留所有权利。
This paper describes the synthesis and biological evaluation of styrylbenzimidazole (SBIM) derivatives as agents for imaging neurofibrillary tangles (NFT) in patients with Alzheimer's disease (AD). SBIM derivatives were prepared with 4-iodobenzene-1,2-diamine and substituted cinnamaldehydes. In binding experiments using recombinant tau and A beta(1-42) aggregates, SBIM-3 showed higher affinity for the tau aggregates than Ab1-42 aggregates (ratio of K-d values was 2.73). In in vitro autoradiography and fluorescent staining, [I-125]SBIM-3 (or SBIM-3) bound NFT in sections of AD brain tissue. In biodistribution experiments using normal mice, all [I-125]SBIM derivatives showed high initial uptake into (3.20-4.11%ID/g at 2 min after the injection) and rapid clearance from (0.12-0.33%ID/g at 60 min after the injection) the brain. In conclusion, appropriate structural modifications of SBIM derivatives could lead to more useful agents for the in vivo imaging of NFT in AD brains. (C) 2013 Elsevier Ltd. All rights reserved.