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

Mengchao Cui, Masahiro Ono, Hiroyuki Kimura, Bo Li Liu, Hideo Saji

Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.

Bioorganic & medicinal chemistry letters 2011 Feb 1

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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. Copyright © 2010 Elsevier Ltd. All rights reserved.

Citation

Mengchao Cui, Masahiro Ono, Hiroyuki Kimura, Bo Li Liu, Hideo Saji. Synthesis and biological evaluation of indole-chalcone derivatives as β-amyloid imaging probe. Bioorganic & medicinal chemistry letters. 2011 Feb 1;21(3):980-2