N-Coumaroyldopamine and N-caffeoyldopamine increase cAMP via beta 2-adrenoceptors in myelocytic U937 cells

N-Caffeoyldopamine is a phytochemical found in various plants, including cocoa (Theobroma cacao L.). N-caffeoyldopamine and its natural analogs (N-cinnamoyldopamine, N-coumaroyldopamine, N-feruloyldopamine, and N-sinapoyldopamine) were synthesized and investigated to determine their potency as P-adrenoceptor agonists, because they have chemical structural moieties found in P-adrenoceptor agonists. Among the compounds tested in this study, N-coumaroyldopamine and N-caffeoyldopamine were the two most potent compounds, able to increase cAMP at the concentrations <0.05 mu M in U937 cells. The decreasing order of potency was N-coumaroyldopamine > N-caffeoyldopamine > N-feruloyldopamine > N-sinapoyldopamine > N-cinnamoyldopamine. Using beta 2-specific antagonists (butoxamine and ICI 118551), N-coumaroyldopamine and N-caffeoyldopamine were found to increase cAMP via beta 2-adrenoceptors in U937 cells. In producing cAMP in U937 cells, N-coumaroyldopamine and N-caffeoyldopamine were as potent as several well-known beta 2-adrenoceptor agonists (salbutamol, procaterol, and fenoterol). These results indicate that N-coumaroyldopamine and N-caffeoyldopamine are potent compounds able to increase cAMP via beta 2-adrenoceptors in U937 cells, and may have potential effects on human health.