New chemical structures of hypolipidemic and antiplatelet activity
Elevated lipid level is supposed to be one of the main risk factors of atherosclerosis and subsequent cardiovascular disease (and is connected to mortality). Therefore, lipid lowering is one of the major targets in cardiovascular disease treatment and prevention. Also, blood platelets play a pivotal role in the development of atherosclerosis and fatal thrombus formation in the course of coronary heart disease. Therefore, there is a great necessity to acquire drugs inhibiting platelet aggregation and clot generation. The present paper reviews new chemical structures in development for the treatment and prevention of hyperlipidemia, atherosclerosis, and subsequent cardiovascular disease. The authors' recent results are also reported regarding synthesis of a new group of a-asarone analogs. These compounds were identified as an original class of agents exhibiting hypolipidemic and antiplatelet (mice, rats) activities. Although the mechanism of the compounds' pharmacological activity has not been identified, quantum-mechanical calculations allowed structural requirements to be described that correspond to the activity (a hypothetical pseudoreceptor structure). Since it is known that asarone and its derivatives may exhibit genotoxicity, calculations were carried out to identify derivatives of possibly low genotoxic activity.