We have synthesized novel asymmetric curcumin and tetrahydrocurcumin derivatives in which one of the phenolic groups has been chemically modified with reactive functional groups: azide, alkyne and carboxylic acid. Using selective azide-alkyne click reaction, we also synthesized a novel curcumin dimer. This is the first report describing a general methodology for preparing asymmetric curcumin derivatives which can be employed to synthesize a variety of biomimetic polyphenols.

Preliminary experiments to test the ability of the curcumin derivatives to dissolve amyloid plaque invitro were performed. The results suggest that the curcumin derivatives reported here show promise in dissolving amyloid plaque, suggesting those moleculars could be used for Alzheimer's disease (AD) therapy.

The ability of the asymmetric curcumin analogs and macromolecular conjugates to destroy Human oligodendroglioma cells have been tested, the analogs show considerable apoptotic activity.

Unlike curcumin, in a caspase activity assay, the curcumin dimer shows selectivity in cell killing: Glial cells which serve as healthy cell live do not undergo apopotosis when treated with dimer. Invivo studies are currently underway in the mouse model.