Design of a Coumarin-Based Fluorescent Probe for Efficient In Vivo Imaging of Amyloid-? Plaques

Cao, Yangyang1,2; Liu, Xiaohui3,4; Zhang, Jingjing3; Liu, Zhongmin1,2; Fu, Yan3; Zhang, Dong3; Zheng, Mingyue3,4; Zhang, Haiyan3,4; Xu, Ming-Hua1,2,5

2023-02-01

10.1021/acschemneuro.2c00468

ACS Chemical Neuroscience   Impact Factor & Quartile

1948-7193

Amyloid-beta (A beta) 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 A beta imaging. By embedding the aromatic coumarin framework into pi bridge of a push-pull chromophore, a novel fluorescence probe XCYC-3 applicable to efficient A beta recognition was discovered. XCYC-3 displays higher fluorescent enhancement for aggregated A beta than monomeric A beta, and possesses good blood-brain barrier permeability. In vitro staining and in vivo imaging studies demonstrated that XCYC-3 could efficiently recognize A beta plaques in the brain of AD transgenic mice. These results suggest that XCYC-3 is a promising fluorescence imaging agent for A beta, which might provide important clues for the future development of potent NIR fluorescent probes for A beta diagnosis.

Alzheimer?s disease fluorescent probe imaging agent Amyloid-? coumarin

SCI

English

First ; Corresponding

Shenzhen Science and Technology Innovation Commission["JCYJ20200109141408054","ZDSYS20190902093215877"] ; Open Fund of Key Laboratory of Receptor Structure and Function, Chinese Academy of Sciences[SIMM2106YKF-02] ; Shanghai Municipal Science and Technology Major Project[2018SHZDZX05] ; Key New Drug Creation and Manufacturing Program?[2018ZX09711002-010-005] ; National Natural Science Foundation of China[82003724]

Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Neurosciences & Neurology

Biochemistry & Molecular Biology ; Chemistry, Medicinal ; Neurosciences

WOS:000928933400001

AMER CHEMICAL SOC

Web of Science

1.Southern Univ Sci & Technol, Shenzhen Grubbs Inst, Shenzhen 518055, Peoples R China
2.Southern Univ Sci & Technol, Dept Chem, Shenzhen Key Lab Small Mol Drug Discovery & Synth, Guangdong Prov Key Lab Catalysis, Shenzhen 518055, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, State Key Lab Drug Res, Shanghai 201203, Peoples R China
4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
5.Henan Normal Univ, Sch Chem & Chem Engn, Xinxiang 453007, Henan, Peoples R China

Cao, Yangyang,Liu, Xiaohui,Zhang, Jingjing,et al. Design of a Coumarin-Based Fluorescent Probe for Efficient In Vivo Imaging of Amyloid-? Plaques[J]. ACS Chemical Neuroscience,2023.

Cao, Yangyang.,Liu, Xiaohui.,Zhang, Jingjing.,Liu, Zhongmin.,Fu, Yan.,...&Xu, Ming-Hua.(2023).Design of a Coumarin-Based Fluorescent Probe for Efficient In Vivo Imaging of Amyloid-? Plaques.ACS Chemical Neuroscience.

Cao, Yangyang,et al."Design of a Coumarin-Based Fluorescent Probe for Efficient In Vivo Imaging of Amyloid-? Plaques".ACS Chemical Neuroscience (2023).