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

Abstract

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 beta-adrenoceptor agonists, because they have chemical structural moieties found in beta-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 microM in U937 cells. The decreasing order of potency was N-coumaroyldopamine > N-caffeoyldopamine > N-feruloyldopamine > N-sinapoyldopamine > N-cinnamoyldopamine. Using beta2-specific antagonists (butoxamine and ICI 118551), N-coumaroyldopamine and N-caffeoyldopamine were found to increase cAMP via beta2-adrenoceptors in U937 cells. In producing cAMP in U937 cells, N-coumaroyldopamine and N-caffeoyldopamine were as potent as several well-known beta2-adrenoceptor agonists (salbutamol, procaterol, and fenoterol). These results indicate that N-coumaroyldopamine and N-caffeoyldopamine are potent compounds able to increase cAMP via beta2-adrenoceptors in U937 cells, and may have potential effects on human health.