Akademik Veri Yönetim Sistemi
Journal of Molecular Structure, cilt.1349, 2026 (SCI-Expanded, Scopus)
Alzheimer's disease is one of the most common neurodegenerative diseases. There is currently no definitive treatment for this disease, which predominantly affects the elderly population. For this reason, discoveries of new molecules are important. Alzheimer's disease is a progressive neurodegenerative disorder involving several pathological mechanisms, notably the reduction of acetylcholine levels and the aggregation of β-amyloid (Aβ) peptides. In this study, novel hybrid compounds derived from donepezil, designed to target both the catalytic active site (CAS) and peripheral anionic site (PAS) of acetylcholinesterase (AChE), were synthesized, and their multifaceted biological activities were evaluated. Among the synthesized derivatives, compounds 4e, 4d, and 4j exhibited remarkable AChE inhibitory potency, with IC50 values of 0.305±0.009 µM, 0.109±0.004 µM, and 0.028±0.001 µM, respectively. Analysis of Aβ plaque inhibition profiles indicated that compound 4j showed a pattern highly like that of donepezil. Furthermore, no toxicity problems were observed with any of the compounds. The obtained results indicate that these new donepezil-derived compounds may be potential multi-target agents against Alzheimer's disease.