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Issue 30, 2020
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Metal-chelating benzothiazole multifunctional compounds for the modulation and 64Cu PET imaging of Aβ aggregation

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Abstract

While Alzheimer's Disease (AD) is the most common neurodegenerative disease, there is still a dearth of efficient therapeutic and diagnostic agents for this disorder. Reported herein are a series of new multifunctional compounds (MFCs) with appreciable affinity for amyloid aggregates that can be potentially used for both the modulation of Aβ aggregation and its toxicity, as well as positron emission tomography (PET) imaging of Aβ aggregates. Firstly, among the six compounds tested HYR-16 is shown to be capable to reroute the toxic Cu-mediated Aβ oligomerization into the formation of less toxic amyloid fibrils. In addition, HYR-16 can also alleviate the formation of reactive oxygen species (ROS) caused by Cu2+ ions through Fenton-like reactions. Secondly, these MFCs can be easily converted to PET imaging agents by pre-chelation with the 64Cu radioisotope, and the Cu complexes of HYR-4 and HYR-17 exhibit good fluorescent staining and radiolabeling of amyloid plaques both in vitro and ex vivo. Importantly, the 64Cu-labeled HYR-17 is shown to have a significant brain uptake of up to 0.99 ± 0.04 %ID per g. Overall, by evaluating the various properties of these MFCs valuable structure–activity relationships were obtained that should aid the design of improved therapeutic and diagnostic agents for AD.

Graphical abstract: Metal-chelating benzothiazole multifunctional compounds for the modulation and 64Cu PET imaging of Aβ aggregation

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Supplementary files

Article information


Submitted
12 May 2020
Accepted
07 Jul 2020
First published
09 Jul 2020

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2020,11, 7789-7799
Article type
Edge Article

Metal-chelating benzothiazole multifunctional compounds for the modulation and 64Cu PET imaging of Aβ aggregation

Y. Huang, H. Cho, N. Bandara, L. Sun, D. Tran, B. E. Rogers and L. M. Mirica, Chem. Sci., 2020, 11, 7789
DOI: 10.1039/D0SC02641G

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