Design Synthesis and Evaluation of Novel Tacrine-Ferulic Acid Hybrids as Multifunctional Drug Candidates against Alzheimer’s Disease

摘要

Five novel tacrine-ferulic acid hybrid compounds (>8a–>e) were synthesized and their structures were identified on the basis of a detailed spectroscopic analysis. The activities of inhibiting acetyl cholinesterase (AChE) and butyryl cholinesterase (BuChE), reducing self-induced β-amyloid (Aβ) aggregation and chelating Cu²⁺ were evaluated in vitro. Among them, >8c and >8d displayed the higher selectivity in inhibiting AChE over BuChE. Moreover, >8d also showed dramatic inhibition of self-Aβ aggregation, activity of chelating Cu²⁺ and activity against Aβ-induced neurotoxicity in Neuro-2A cells.