Synthesis and biological evaluation of indole-chalcone derivatives as β-amyloid imaging probe

✍ Scribed by Mengchao Cui; Masahiro Ono; Hiroyuki Kimura; Bo Li Liu; Hideo Saji

• Book ID: 104005226
• Publisher: Elsevier Science
• Year: 2011
• Tongue: English
• Weight: 468 KB
• Volume: 21
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/j.bmcl.2010.12.045

✦ Synopsis

A series of chaclone derivatives containing an indole moiety were evaluated in competitive binding assays with Aβ(1-42) aggregates versus [(125)I]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 Aβ plaques within brain sections of AD transgenic mice. The radioiodinated probe [(125)I]-(E)-3-(1H-indol-5-yl)-1-(4-iodophenyl)prop-2-en-1-one, [(125)I]4, was prepared and autoradiography in sections of brain tissue from an animal model of AD showed that it labeled Aβ plaques specifically. However, experiments with normal mice indicated that [(125)I]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 β-amyloid plaques in the brains of AD patients.