Synthesis of Curcumin Analogues to Increase Bioavailabilty and Determination of Anti-Mitotic and ß-Secretase Inhibition Properties

Curcumin, the yellow coloring component of tumeric has been found to have anti-oxidative, anti-mitotic, and anti-inflammatory action in vitro.  It has also has been shown to inhibit ß-secretase, the enzyme thought responsible for the accumulation of plaque in the brain and onset of Alzheimer's disease. Unfortunately, curcumin is not naturally water soluble and thus has low levels of bioavailability.  By alkylating curcumin with nitrogen containing groups, it is possible to increase its solubility while maintaining its anti-oxidant and anti-inflammatory properties.  Synthesis is approached from two routes: Either alkylating a complete curcumin molecule with the nitrogen groups directly, or synthesis of multiple diketone curcumin molecule, both of which are carried out under reflux conditions.  We have successfully ascertained mono and doubly alkylated analogues of curcumin. These analogues will be subjected to tubulin testing in HeLa cells and to quantify the extent of their anti-mitotic properties.  Our goal is to quanitfy the power of curcumin analogues and add it as a low cost weapon in the medical arsenal against cancer and alzheimer's disease.