Department of Pharmaceutical Botany and Ecology, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
Biochimie. 2012 Dec;94(12):2681-6. doi: 10.1016/j.biochi.2012.09.006. Epub 2012 Sep 17.
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.
血小板在生理止血中起着至关重要的作用。然而，在动脉粥样硬化损伤的冠状动脉中，增强的血小板聚集，随后形成血栓，是急性心肌梗死的一个促成因素。目前的治疗方法能够减少大约四分之一的心血管事件，但它们与出血风险增加有关，并且在一些耐药患者中效率不高。一些香豆素具有抗血小板活性，并且由于其额外的抗氧化作用，可能是与目前治疗药物联合使用的有前途的药物。本研究旨在分析一系列简单的 4-甲基香豆素的抗血小板活性。用人血浆血小板悬浮液用不同的诱导剂[花生四烯酸（AA）、胶原和 ADP]在 4-甲基香豆素存在下进行处理。进行了补充实验以解释作用机制。5,7-二羟基-4-甲基香豆素，特别是那些在 C-3 位具有亲脂侧链的香豆素，对 AA 诱导的聚集具有与乙酰水杨酸相当的活性。其他测试的香豆素活性较低。一些测试的化合物轻度抑制胶原或 ADP 诱导的聚集。5,7-二羟基-4-甲基香豆素不干扰血栓素合酶的功能，但对血栓素 A2 受体是竞争性拮抗剂，并抑制环加氧酶-1。5,7-二羟基-4-甲基香豆素似乎是扩展当前抗血小板药物谱的有前途的候选药物。
