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

Xuyi Yue, Dhruva D. Dhavale, Junfeng Li, Zonghua Luo, Jialu Liu, Hao Yang, Robert H. Mach, Paul T. Kotzbauer, Zhude Tu

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageEnglish
Pages (from-to)1011-1019
Number of pages9
JournalBioorganic and Medicinal Chemistry Letters
Volume28
Issue number6
DOIs
StatePublished - Apr 1 2018

Keywords

  • PET radiotracer
  • Parkinson's disease
  • Quinolinyl analogue
  • Radiosynthesis
  • Thioflavin T fluorescence assay
  • α-Synuclein fibrils

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