Abstract A novel series of benzylisoquinoline derivatives were designed, synthesized, and evaluated as multifunctional agents against Alzheimer's disease (AD). The screening results showed that most of the compounds significantly inhibited cholinesterases (ChEs), human cholinesterases (h-ChEs) and self-induced β-amyloid (Aβ) aggregation. In particular, compound 9k showed the strongest acetylcholinesterase (AChE) inhibitory activity, being ...