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Deposition of α-synuclein (α-syn) aggregates is one of the neuropathological hallmarks of synucleinopathies including Parkinson's disease, dementia with Lewy bodies, and multiple-system atrophy. In vivo detection of α-syn aggregates with SPECT or PET may be an effective tool for medical intervention against synucleinopathy. In the present study, we designed and synthesized a series of chalcone analogues with different aryl groups to evaluate their potential as α-syn imaging probes. In competitive inhibition assays, aryl groups markedly affected binding affinity and selectivity for recombinant α-syn aggregates. Chalcone analogues with a 4-(dimethylamino)phenyl group bound to both α-syn and amyloid β (Aβ) aggregates while ones with a 4-nitrophenyl group displayed α-syn-selective binding. In fluorescent staining, only chalcone analogues with a 4-nitrophenyl group succeeded in selective detection of human α-syn against Aβ aggregates in patients' brain samples. Among them, PHNP-3 exhibited the most promising binding characteristics for α-syn aggregates ( |
