Development of novel chalcone derivatives as multifunctional agents for the treatment of Alzheimer ’s disease

AbstractTo develop multifunctional agents for the treatment of Alzheimer ’s disease (AD), a series of novel chalcone derivatives was developed as the multitarget-directed ligands. Their MAOs inhibitory activities, anti-inflammation properties and neuroprotective effects were evaluated in vitro. The results showed that most of the synthetic compounds exhibited good sele ctive MAO-B inhibitory activity. Among them, compound3i exhibited the best MAO-B inhibitory potency with IC50 values of 0.092  μM, and the molecular docking provide possible mechanism for its high MAO-B inhibitory potency. Compound3i also significantly inhibited self-induced Aβ1-42 aggregation. Moreover, compound3i showed significant anti-inflammation property and good neuroprotective effects on Glu-/Aβ25-35-induced PC12 cell injury. Furthermore, compound3i showed favorable ADME properties. Thus, the results suggest that compound3i was a promising multifunctional agent against AD.
Source: Medicinal Chemistry Research - Category: Chemistry Source Type: research