Design, Synthesis, and in Vitro Evaluation of Quinolinyl Analogues for α-synuclein Aggregation

Overview

Journal Bioorg Med Chem Lett

Specialty Biochemistry

Date 2018 Feb 28

PMID 29482941

Citations 7

Authors

Xuyi Yue

Dhruva D Dhavale

Junfeng Li

Zonghua Luo

Jialu Liu

Hao Yang

Robert H Mach

Paul T Kotzbauer

Zhude Tu

Affiliations

Soon will be listed here.

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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