Design, synthesis, and in vitro evaluation of quinolinyl analogues for α-synuclein aggregation

Bioorganic & Medicinal Chemistry Letters
Xuyi YueZhude Tu

Abstract

Here we report the synthesis and in vitro evaluation of 25 new quinolinyl analogues for α-synuclein aggregates. Three lead compounds were subsequently labeled with carbon-11 or fluorine-18 to directly assess their potency in a direct radioactive competitive binding assay ng both α-synuclein fibrils and tissue homogenates from Alzheimer's disease (AD) cases. The modest binding affinities of these three radioligands toward α-synuclein were comparable with results from the Thioflavin T fluorescence assay. However, all three ligand also showed modest binding affinity to the AD homogenates and lack selectivity for α-synuclein. The structure-activity relationship data from these 25 analogues will provide useful information for design and synthesis of new compounds for imaging α-synuclein aggregation.

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Citations

Dec 29, 2020·European Journal of Nuclear Medicine and Molecular Imaging·Laura KueblerKristina Herfert
Mar 4, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sana YaqoobFarooq-Ahmad Khan
May 12, 2018·ACS Chemical Neuroscience·Chia-Ju HsiehRobert H Mach

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