Aminoalkyl-substituted flavonoids: synthesis, cholinesterase inhibition, β-amyloid aggregation, and neuroprotective study

In this manuscript, 17 aminoalkyl-substituted flavonoid derivatives were synthesized and their anticholinesterase, anti-beta-amyloid (A) aggregation and neuroprotective activities were evaluated. The synthesized compounds were prepared through four-step reaction, started from the reaction between 2-hydroxyacetophenone and 4-methoxy benzaldehyde. Among the final compounds, 6j displayed the best anti-butyrylcholinesterase activity (IC50=0.335M). Moreover, compound 6i significantly protected PC12 neurons against H2O2-induced cell death. This compound could also inhibit acetylcholinesterase and self-induced A peptide aggregation by 51.3% and 49.2%, respectively. The results indicated that compound 6i could be considered as a lead compound towards the discovery of disease-modifying drugs for Alzheimer's disease (AD) therapy.