Multifunctional coumarin derivatives: Monoamine oxidase B (MAO-B) inhibition, anti-β-amyloid (Aβ) aggregation and metal chelation properties against Alzheimer’s disease

Abstract A series of coumarin derivatives were designed, synthesized, and evaluated as novel multifunctional agents against Alzheimer’s disease (AD). In vitro studies showed that most of these compounds exhibited significant potency to inhibit h MAO-B selectively and self-induced Aβ 1–42 aggregation. In particular, compound 13 presented the greatest potential to inhibit h MAO-B (IC 50  = 0.081 μM, SI >1234) and good inhibition of Aβ 1–42 aggregation (52.9% at 20 μM). Moreover, compound 13 could function as a metal-chelator, penetrate the blood–brain barrier (BBB) and show low cell toxicity in rat pheochromocytoma (PC12) and SH-SY5Y cells. Taken together, these results suggested that compound 13 might be a promising multifunctional agent for AD treatment.