Design, synthesis and biological evaluation of imine resveratrol derivatives as multi-targeted agents against Alzheimer's disease.

A series of imine resveratrol derivatives (1-20) have been designed, synthesized, and evaluated as multi-targeted compounds for the treatment of Alzheimer's disease (AD). In vitro studies show that most of the molecules exhibit a significant ability to inhibit self-induced and Cu(2+)-induced β-amyloid (Aβ₁₋₄₂) aggregation, and to function as potential antioxidants and biometal chelators. In particular, compound 9 is a potential lead compound for AD treatment (for compound 9, IC₅₀ = 14.1 μM for the antioxidant activity using DPPH free radical method; 64.6% at 20 μM for self-induced Aβ aggregation). Moreover, it is capable of decreasing reactive oxygen species (ROS) induced by Cu-Aβ and shows good neuroprotective effects in human SH-SY5Y neuroblastoma cells. Taken together, these results suggest that 9 might be a promising lead compound for AD treatment.