The spice turmeric has a history of medicinal use and is believed to contribute to good health when consumed regularly. Curcumin, a component of turmeric, has exhibited a wide array of in vitro activities and has attracted particular interest due to its anti-oxidative and anti-inflammatory action. It has also been tested clinically for its effects on cognitive impairment and Alzheimer's disease though it was found to have very low bioavailability. During our studies to discover new compounds for the prevention of neurodegeneration we were surprised to find an analogue of curcumin to be a weak inhibitor of the beta-secretase enzyme. Molecular modeling and docking suggested that the highly enolizable 1,3-diketone might bind to the aspartic acid side chain carboxylates in the active site. We have prepared variously substituted amine-containing curcumin analogues in an effort to explore this binding hypothesis and to find novel beta-secretase inhibitors with improved solubility and metabolic properties. A limited structure-activity relationship will be reported.