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

A series of novel indole-chalcone derivatives were synthesized and evaluated as Aβ imaging probes. A series of chaclone derivatives containing an indole moiety were evaluated in competitive binding assays with Aβ 1-42 aggregates versus [ 125I]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 [ 125I]-( E)-3-(1 H-indol-5-yl)-1-(4-iodophenyl)prop-2-en-1-one, [ 125I] 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 [ 125I] 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.