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

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.