Rhodanine composite fluorescence probes to detect amyloid-beta aggregated species in Alzheimer's disease models

AbstractMolecular near-infrared (NIR) imaging is an emerging pre-clinical tool for labeling Alzheimer's disease (AD) pathogenic biomarkers, especially cerebral amyloid-beta (Aβ) plaques. Herein, we present a series of acceptor-π-donor based molecular NIR probes, composed of rhodanine (acceptor fragment) in conjugation with coumarin or carbostyril (donor fragment) nucleus. The most promising probe19has a desirable binding affinity (Kd= 0.143 μM) against Aβ aggregates with little or no nonspecific interaction with BSA, minimal cytotoxicity, good brain permeability, desirable plasma stability, and fluorescence sustainability profile across a comprehensive physiological pH range. Histological fluorescence imaging revealed that probe19had good selectivity and affinity for Aβ plaques, confirmed with immunofluorescence and ThT (aggregated Aβ specific dye), and a high signal-to-noise ratio. It was also successfully applied for fluorescence labeling of Aβ in the eye imaginal disc of AD Drosophila larvae. Collectively, these probes can be finetuned due to their versatile structural scaffold to evolve as promising NIR imaging probes for the detection of AD biomarkers.