Design, synthesis, and biological evaluation of curcumin analogues as multifunctional agents for the treatment of Alzheimer’s disease

A series of novel curcumin analogues were designed, synthesized, and biologically evaluated as multifunctional agents targeting β-amyloid, oxidative stress, and redox-active metal ions. Compound A4 was found to have the most potent Aβ aggregation inhibitory activity (IC50=2.5μM). A series of novel curcumin analogues were designed, synthesized, and evaluated as potential multifunctional agents for the treatment of AD. The in vitro studies showed that these compounds had better inhibitory properties against Aβ aggregation than curcumin. Superior anti-oxidant properties (better than the reference compound Trolox) of these compounds were observed by the oxygen radical absorbance capacity (ORAC) method and a cell-based assay using DCFH-DA as a probe. In addition they were able to chelate metals such as iron and copper and decrease metal-induced Aβ aggregation. The structure–activity relationships were discussed. The results suggested that our curcumin analogues could be selected as multifunctional agents for further investigation of AD treatment.