Resveratrol-maltol hybrids as multi-target-directed agents for Alzheimer's disease.

The 3-hydroxypyran-4-one moiety (maltol) was incorporated into the structure of resveratrol to achieve a series of resveratrol-maltol hybrids (8a-8k) as novel multi-target-directed ligands (MTDLs). In vitro biological evaluation of the MTDLs revealed these compounds to have a triple function, namely inhibition of self-induced Aβ1-42 aggregation, antioxidation, and metal chelating activity. Among all the evaluated MTDLs, compounds 8i and 8j showed the most promise, demonstrating micromolar IC50 values for Aβ1-42 aggregation inhibition, more potent ABTS+ scavenging activity than Trolox, and good metal chelating activities.