Design and Evaluation of Quinoline-derived Fluorophores for Labeling Amyloid Beta 1-42 in Alzheimer's Disease

Amyloid beta (Aβ) is a key biomarker in Alzheimer's disease, driving the formation of senile plaques that contribute to neuronal death within a complex etiology. Typically, most treatments begin at advanced stages, when irreversible brain atrophy has already occurred; therefore, early diagnosis is essential for effective intervention. Several probes based on the conventional donor-π-acceptor (D-π-A) structural motif have been developed as diagnostic tools, yet few have reached clinical trials. Alternatively, quinoline-based fluorescent compounds with push-pull structures and aggregation-induced emission properties show enhanced fluorescence in the aggregated state due to restricted intramolecular motion (RIM). Accordingly, four quinoline derivatives2QnCN, 3QnCN, 3QnB, and 4QnBBwere synthesized using standard methods, including benzoxazole segments and a cyano (-CN) group. They were chemically and optically characterized, and their photophysical properties were calculated. Theoretical analyses include band gap estimation and visualization of intramolecular charge transfer. Molecular docking was also performed to assess binding with the Aβ(1-42) pentamer (PDB: 2BEG), identifying 3QnCN as the most promising candidate with a binding energy of-11.9 kcal/mol. Cytotoxicity was tested using the MTT assay to determine the optimal working concentration. The fluorescence intensity of 3QnCN in PC12 cells was quantified, and confocal microscopy confirmed its effectiveness in labeling Aβ(1-42).