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 A(2) 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.

• MeSH
• adenosindifosfát farmakologie   MeSH
• agregace trombocytů účinky léků   MeSH
• antikoagulancia chemie   farmakologie   MeSH
• Aspirin farmakologie   MeSH
• cyklooxygenasa 1 metabolismus   MeSH
• inhibitory agregace trombocytů chemie   farmakologie   MeSH
• inhibitory cyklooxygenasy farmakologie   MeSH
• kolagen farmakologie   MeSH
• kumariny chemie   farmakologie   MeSH
• kyselina arachidonová farmakologie   MeSH
• lidé MeSH
• molekulární struktura MeSH
• preklinické hodnocení léčiv metody   MeSH
• receptory pro thromboxan A2, prostaglandin H2 antagonisté a inhibitory   metabolismus   MeSH
• thromboxan-A synthasa antagonisté a inhibitory   metabolismus   MeSH
• umbeliferony chemie   farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH