2007 Annual Report 1a.Objectives (from AD-416) 1) To synthesize N-coumaroyltyramine and its analogues and to identify their cellular effects and molecular mechanisms, particularly as related to cancer modulation,. 2)To assess anti-cancer and other health effects N-coumaroyltyramine and its analogues in an animal model. 1b.Approach (from AD-416) 1. Synthesis of phenylpropenic acid conjugates (N-coumaroyltyramine and its analogues). 2. Measurement of phenylpropenic acid conjugates in cell and biological samples. 3. Investigation of effects of phenylpropenic acid conjugates on cell cycle and growth of cancer cells. 4. Apoptosis study. 5. Hydrogen peroxide quenching study. 6. Investigation of effects of phenylpropenic acid conjugates on MAPK Kinases. 7. Investigation of effects of phenylpropenic acid conjugates on protein tyrosine kinase including EGFR. 8. Investigation of effects of phenylpropenic acid conjugates on xenograft tumor in nude mice. 3.Progress Report The lead scientist established a Phytochemical Database: that provides information on phytochemicals, medicinal plants, herbs and spices, medicines, and supplements that have phyochemicals as a basic ingredient. The website provides information and links to additional data on studies that show the interaction between phytochemical composition in the diet and conditions such as obesity, diabetes, aging, hypertension, heart disease, and inflammation. 4.Accomplishments Synthesized of Clovamide-type Polyphenols to Evaluate Anti-inflammatory Properties in Animal Models: More than 50 clovamide-type phenylpropenoic acid amides found in coffee, cocoa, tea, and other plant sources were synthesized, purified, and investigated to determine their effects on P-selectin expression and platelet-leukocyte interactions found in blood cells. N-caffeoyldopamine and N-caffeoyltyramine were the most potent phenolic conjugates in blood cells, inhibiting P-selectin expression and platelet-leukocyte interactions in vitro and in vivo models. N-caffeoyldopamine and N-caffeoyltyramine were found to contain both COX inhibitory and cAMP producing activities which are key inflammatory mediators. The dual activities of these compounds suggests that they may be important in preventing human cardiovascular and inflammatory diseases that are treated typically with drugs that are COX inhibitors that often cause adverse effects. In addition, the bioavailability of safflomide (a phenolic conjugate) was determined for the first time using mouse models. This research addresses Component 5 of the National Program 107 Action Plan: “Identifying the Health Promoting Properties of Plant and Animal Foods”. 5.Significant Activities that Support Special Target Populations None 6.Technology Transfer Number of new CRADAs and MTAs 1 Number of invention disclosures submitted 1 Number of web sites managed 1 Review Publications Park, J.B. 2007. Caffedymine from cocoa has COX inhibitory activity suppressing the expression of a platelet activation marker, P-selectin. Journal of Agricultural and Food Chemistry.(6):2171-5. Park, J.B., Chen, P. 2007. Synthesis of safflomide and its HPLC measurement in mouse plasma after oral administration. Journal of Chromatography B: Biomedical Applications. 852(1-2):398-402.