Structure-activity relationship of chalcones and related derivatives as ligands for detecting of beta-amyloid plaques in the brain.
A series of novel chalcones and their related derivatives were synthesized and evaluated as beta-amyloid imaging probes. In the structure-activity relationship of binding affinities to synthetic Abeta(1-42) aggregates, compound 14 displayed the highest binding affinity in vitro. beta-Amyloid plaques in the Alzheimer's model mouse brain were visualized with 14. In biodistribution studies using normal mice, [(125)I]14 showed good brain uptake (2.56% ID/g, 2min postinjection) and rapid washout from the brain (0.21% ID/g, 60min postinjection). These results suggest that [(125)I]14 should be further investigated as a potentially useful beta-amyloid imaging probe.
Ono
Masahiro
M
Department of Hygienic Chemistry, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan. mono@nagasaki-u.ac.jp
Hori
Miyuki
M
Haratake
Mamoru
M
Tomiyama
Takami
T
Mori
Hiroshi
H
Nakayama
Morio
M
D000544:Alzheimer Disease / Q000188:drug therapy / Q000473:pathology; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D047188:Chalcones / Q000138:chemical synthesis / Q000494:pharmacology*; D004195:Disease Models, Animal; D008024:Ligands; D051379:Mice; D058225:Plaque, Amyloid / Q000378:metabolism*; D013329:Structure-Activity Relationship
D047188:Chalcones; D008024:Ligands