Structure–activity relationship of chalcones and related derivatives as ligands for detecting of β-amyloid plaques in the brain

Abstract

A series of novel chalcones and their related derivatives were synthesized and evaluated as β-amyloid imaging probes. In the structure–activity relationship of binding affinities to synthetic Aβ(1–42) aggregates, compound 14 displayed the highest binding affinity in vitro. β-Amyloid plaques in the Alzheimer’s model mouse brain were visualized with 14. In biodistribution studies using normal mice, [ 125I] 14 showed good brain uptake (2.56% ID/g, 2 min postinjection) and rapid washout from the brain (0.21% ID/g, 60 min postinjection). These results suggest that [ 125I] 14 should be further investigated as a potentially useful β-amyloid imaging probe.