New chemical structures of hypolipidemic and antiplatelet activity*
Z. Chilmonczyk1,2,#, D. Siluk3, R. Kaliszan3, B. L/ozowicka2, J. Popl/awski2,
and S. Filipek4
1Drug Institute, Chel/mska 30/34, 00-725 Warsaw, Poland;
2Institute of Chemistry, University of Bial/ystok, J. Pil/sudskiego
11/4, 15-443 Bial/ystok, Poland; 3Department of Biopharmaceutics and
Pharmacodynamics, Medical University of Gdan´sk, Gen. J. Hallera
107, 80-416 Gdan´sk, Poland; 4Department of Chemistry, University
of Warsaw, 1 Pasteura St., 02-093 Warsaw, Poland
Abstract: 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.
*Plenary lecture presented at the Hungarian-German-Italian-Polish
Joint Meeting on Medicinal Chemistry, Budapest, Hungary, 2 –6 September
2001. Other presentations are published in this issue, pp.
1387-1509.
# Corresponding author.
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