Design, synthesis, and in vitro evaluation of quinolinyl analogues for α-synuclein aggregation. Issue 6 (1st April 2018)

• Record Type: Journal Article
• Authors: Yue, Xuyi; Dhavale, Dhruva D.; Li, Junfeng; Luo, Zonghua; Liu, Jialu; Yang, Hao; Mach, Robert H.; Kotzbauer, Paul T.; Tu, Zhude
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 28:Issue 6(2018)
• Page Start: 1011
• Page End: 1019
• Publication Date: 2018-04-01
• Subjects: α-Synuclein fibrils -- Quinolinyl analogue -- Radiosynthesis -- PET radiotracer -- Thioflavin T fluorescence assay -- Parkinson's disease; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2018.02.031
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: 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.