Chem. Pharm. Bull. 52(6) 696—699 (2004)

pathogenesis of various circulatory and neurodegenerative disorders such as thrombosis, atherosclerosis and Alzheimer’s disease, which is now thought to have an inflammatory base. The development of antiinflammatory agents which prevent the accumulation of leucocytes, platelet activation or lost of function of the vessel wall, could constitute new therapeutic strategies for the control of these and others inflammatory diseases. Interestingly aporphines and phenanthrene alkaloids have been shown to exert a strong antiplatelet and vasorelaxing effects. In this context, the aporphine boldine can inhibit the aggregation of rabbit platelets induced by arachidonic acid and collagen but it did not affect to the platelet aggregation induced by platelet activating factor (PAF), thrombin or a tromboxane analog U46619. Conversely, its corresponding phenanthrene alkaloid secoboldine, in addition to arachidonic acid and collagen, it can also inhibit the platelet aggregation induced by PAF or U46619. Furthermore, some aporphine and phenanthrene alkaloids have been shown to inhibit PAF binding to its receptor. In this study it was suggested that the piperidine ring (ring B) of the aporphine skeleton may not be important for PAF antagonisms from the established structure–activity relationship. On the other hand, studies investigating the potential vasorelaxing activity of these type of alkaloids demonstrated that phenanthrene alkaloids with a tertiary amine or N-oxide and two methoxy groups or a methylenedioxy group at C-3 and C-4 (ring A), were the most potent vasorelaxing agent. In contrast, when the substituent group at C-6 and C-7 in ring C are both methoxy groups vasorelaxing action was reduced. Therefore, the aim of the present study is to synthesize phenanthrene alkaloids with secondary, tertiary or quaternary amine from boldine as starting material with oxygenated substituents in C-3 and C-4 (ring A) and with or without both methoxy groups at C-6, C-7 (ring C). Despite this class of compounds may inhibit platelet aggregation or behave as vasorelaxing agents, little is known about their antioxidant properties. Since ROS are involved in both platelet aggregation and vessel wall reactivity, and we have recently found that phenanthrene alkaloids can exert antiinflammatory activity through inhibition of ROS generation, we have evaluated the possible antioxidant activity of these compounds by two different methods. Thus, they may have a potential use as antiinflammatory agents.