Kinetic studies of the addition of thiolate and amine nucleophiles to Curcumin

CHED 426

Argentina Ornelas, aornelas@csupomona.edu, Department of Chemistry, California State Polytechnic University, Pomona, 3801 W. Temple Ave., Pomona, CA 91768
Curcumin is the active ingredient in curry that has been shown to inhibit the enzyme aminopeptidase N (APN), an enzyme that promotes angiogenesis. It is postulated that curcumin's activity stems from a Michael-type reaction of nucleophilic aminoacids in APN's active site and the (beta)-carbons of curcumin. The proposed research project is to measure the kinetics of nucleophilic attack of a model thiol nucleophile on the (beta)-carbon of curcumin. The rate of reaction between L-cysteine as the model amino acid nuclephile and curcumin will also be measured in 100%H2O. Reaction will be followed by monitoring the loss of curcumin overtime by conventional UV-Vis spectroscopy(biological pH), or by stopped flow spectroscopy (thiolate as its own buffer). This project will serve as the biginning point for a larger structure-reactivity study. In this latter study the effect of ring substitution on the reactivity of the (beta)-carbon toward thiol nucleophile attack will be measure kinetically.