Alzheimer's disease (AD) is a multifaceted neurodegenerative disorder for which the underlying causes remain largely unknown. Therefore, the development of imaging agents capable of detecting biomarkers associated with this disease is crucial. Dual-functional probes are particularly important as they can track two biomarkers at the same time and examine their interaction. Herein, Two red-emissive dual-functional fluorescent probes, RC-1 and RA-2, have been designed and synthesized based on the Rofecoxib scaffold. When probes (RC-1 and RA-2) are in viscous media or bound to Aβ aggregates, there is a dramatic enhancement in fluorescence emission due to the constraint of the twisted intramolecular charge transfer effect (TICT). RC-1 with ideal blood-brain barrier (BBB) penetrability enables visualization of Aβ plaques in vivo AD mice. These results suggest that RC-1 and RA-2 have the potential to serve as powerful fluorescence imaging agents for Aβ and mitochondria-related pathology in AD.
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http://dx.doi.org/10.1016/j.saa.2023.123637 | DOI Listing |
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