Metal-Chelating Benzothiazole Multifunctional Compounds for the Modulation and 64Cu PET Imaging of Aβ Aggregation

05 June 2020, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


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 Ab aggregation and its toxicity, as well as positron emission tomography (PET) imaging of Ab aggregates. Firstly, among the six compounds tested HYR-16 is shown to be capable to reroute the toxic Cu-mediated Ab 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/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.


Alzheimer’s disease and Related Diseases
amyloid plaques
multifunctional compounds
PET imaging
SAR studies

Supplementary materials



Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.