In?vitro platelet antiaggregatory properties of 4-methylcoumarins

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• 作者：Kate?ina Macá ; ková ; ^a ; Zuzana ?ehá ; ková ; ^a ; P?emysl Mlad¨§nka^b ; ^{mladenkap@faf.cuni.cz} ; Jana Karlí ; ?ková ; ^a ; Tomá ; &scaron ; Filipský ; ^b ; Michal ?í ; ha^b ; Ashok K. Prasad^c ; Virinder S. Parmar^c ; Lud¨§k Jahodá ; ?^a ; Petr Pá ; vek^b ; Radomí ; r Hrdina^b ; Luciano Saso^d
• 关键词：Coumarins ; Platelet ; Antiaggregatory ; Acetylsalicylic acid ; Arachidonic acid
• 刊名：Biochimie
• 出版年：2012
• 出版时间：December, 2012
• 年：2012
• 卷：94
• 期：12
• 页码：2681-2686
• 全文大小：484 K

文摘

Platelets play a crucial role in physiological haemostasis. However, in coronary arteries damaged by atherosclerosis, enhanced platelet aggregation, with subsequent thrombus formation, is a precipitating factor in acute myocardial infarction. Current therapeutic approaches are able to reduce approximately one quarter of cardiovascular events, but they are associated with an increased risk of bleeding and in some resistant patients are not efficient. Some coumarins possess antiplatelet activity and, due to their additional antioxidant effects, may be promising drugs for use in combination with the present therapeutic agents.

The aim of this study was to analyse a series of simple 4-methylcoumarins for their antiplatelet activity. Human plasma platelet suspensions were treated with different aggregation inducers [arachidonic acid (AA), collagen and ADP] in the presence of the 4-methylcoumarins. Complementary experiments were performed to explain the mechanism of action.

5,7-Dihydroxy-4-methylcoumarins, in particular those containing a lipophilic side chain at C-3, reached the activity of acetylsalicylic acid on AA-induced aggregation. Other tested coumarins were less active. Some of the tested compounds mildly inhibited either collagen- or ADP-induced aggregation. 5,7-Dihydroxy-4-methylcoumarins did not interfere with the function of thromboxane synthase, but were competitive antagonists of thromboxane A₂ receptors and inhibited cyclooxygenase-1 as well.

5,7-Dihydroxy-4-methylcoumarins appear to be promising candidates for the extension of the current spectrum of antiplatelet drugs.