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) were designed and synthesized.
• Most of the compounds could function as antioxidants and inhibit Aβ aggregation.
• Most of the compounds showed neuroprotection and metal chelating ability.
• 9 was found to be a promising lead compound for further study.

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 Cu2+-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.

A series of imine resveratrol derivatives were designed, synthesized, and evaluated as multi-targeted compounds for the treatment of AD. 9 might be a promising compound for further study.Figure optionsDownload as PowerPoint slide