Design of a Coumarin-Based Fluorescent Probe for Efficient Imaging of Amyloid-β Plaques.

ACS Chem Neurosci

Shenzhen Grubbs Institute and Department of Chemistry, Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen 518055, China.

Published: March 2023

Amyloid-β (Aβ) is the core constituent protein of senile plaques, which is one of the key pathological hallmarks of Alzheimer's disease (AD). Here we describe the design, synthesis, and evaluation of coumarin-derived small molecule fluorophores for Aβ imaging. By embedding the aromatic coumarin framework into π bridge of a push-pull chromophore, a novel fluorescence probe applicable to efficient Aβ recognition was discovered. displays higher fluorescent enhancement for aggregated Aβ than monomeric Aβ, and possesses good blood-brain barrier permeability. staining and imaging studies demonstrated that could efficiently recognize Aβ plaques in the brain of AD transgenic mice. These results suggest that is a promising fluorescence imaging agent for Aβ, which might provide important clues for the future development of potent NIR fluorescent probes for Aβ diagnosis.

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Source
http://dx.doi.org/10.1021/acschemneuro.2c00468DOI Listing

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