title: Synthesis and biological evaluation of indole-chalcone derivatives as β-amyloid imaging probe.
abstract: 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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors.forename: Mengchao
authors.initials: M
authors.lastname: Cui
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ono
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kimura
authors.forename: Bo Li
authors.initials: BL
authors.lastname: Liu
authors.forename: Hideo
authors.initials: H
authors.lastname: Saji
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D002599:Chalcone / Q000138:chemical synthesis / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000737:chemistry; D007211:Indoles / Q000737:chemistry*; D007457:Iodine Radioisotopes / Q000737:chemistry; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D011720:Pyrazoles / Q000737:chemistry; D011877:Radionuclide Imaging; D014018:Tissue Distribution
chemical_list: D016229:Amyloid beta-Peptides; D005456:Fluorescent Dyes; D007211:Indoles; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D011720:Pyrazoles; C075222:amyloid beta-protein (1-42); D002599:Chalcone; C000971:2,3-dihydro-1H-imidazo(1,2-b)pyrazole