Cholinesterase (ChE) and secretase (BACE) inhibitors, and fibril- and β-amyloid-suppressing medicines are used to treat Alzheimer's disease (AD) symptomatically. The prevalence and complex nature of AD have increased the urgent need for multi-targeted directed ligands (MTDLs). This is because MTDLs can prevent potential drug-drug interactions during poly-therapy and have a better therapeutic profile than single targeted agents. Using piperazine linker or spacer and two primary scaffolds, benzofuran and 8-hydroxyquinoline, a unique class of multi-targeted medicines was recently reported by our group. These compounds showed re-markable effectiveness in inhibiting Aβ1-42 aggregation and acting as iron chelators.The results prompted us to synthesize an additional series of compounds as multimodal anti-AD agents and investigate its inhibitor activities to ChE (AChE/BChE) and BACE1 enzymes. The resulting in-hibitory effects suggested that the compounds under study might be used to improve cognitive function. The docking analysis' findings revealed that the compounds bind to AChE and BChE by forming H-bond interactions with amino acid residues at binding sites and µ-stacking inter-actions with aromatic residues, whereas the binding to BACE1 only revealed H-bond interac-tions with amino acid residues at binding sites.