Synthesis and biological evaluation of indole-chalcone derivatives as β-amyloid imaging probe
Synthesis and biological evaluation of indole-chalcone derivatives as β-amyloid imaging probe
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DOI：
10.1016/j.bmcl.2010.12.045
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发表时间：
2011-02-01
影响因子：
2.7
通讯作者：
Saji, Hideo
中科院分区：
文献类型：
--
作者：
Cui, Mengchao;Ono, Masahiro;Saji, Hideo
在A β（1-42）聚集体与[I-125]IMPY的竞争性结合试验中评价了一系列含有吲哚部分的查克隆衍生物。这些化合物的亲和力范围为4.46至> 1008 nM，取决于苯环上的取代。体外荧光染色显示，一种具有N，N-二甲基氨基的化合物强烈染色AD转基因小鼠脑切片内的A β斑块。制备了放射性碘标记的探针[I-125]-（E）-3-（1H-吲哚-5-基）-1-（4-碘苯基）丙-2-烯-1-酮，[I-125]4，在AD动物模型脑组织切片中的放射自显影显示它特异性标记A β斑块。然而，正常小鼠的实验表明，[I-125]4在体内脑中的摄取较低（2 min时为0.41% ID/g）。这种吲哚-查耳酮结构的额外化学修饰可能导致更有用的成像剂用于检测AD患者大脑中的β-淀粉样蛋白斑块。(C)2010爱思唯尔有限公司保留所有权利。
A series of chaclone derivatives containing an indole moiety were evaluated in competitive binding assays with A beta(1-42) aggregates versus [I-125]IMPY. The affinity of these compounds ranged from 4.46 to > 1008 nM, depending on the substitution on the phenyl ring. Fluorescent staining in vitro showed that one compound with a N,N-dimethylamino group intensely stained A beta plaques within brain sections of AD transgenic mice. The radioiodinated probe [I-125]-(E)-3-(1H-indol-5-yl)-1-(4-iodophenyl)prop-2-en-1-one, [I-125]4, was prepared and autoradiography in sections of brain tissue from an animal model of AD showed that it labeled A beta plaques specifically. However, experiments with normal mice indicated that [I-125]4 exhibited a low uptake into the brain in vivo (0.41% ID/g at 2 min). Additional chemical modifications of this indole-chalcone structure may lead to more useful imaging agents for detecting beta-amyloid plaques in the brains of AD patients. (C) 2010 Elsevier Ltd. All rights reserved.