Platelets are the critical target for preventing and treating pathological thrombus formation. However, despite current antiplatelet therapy, cardiovascular mortality remains high, and cardiovascular events continue in prescribed patients. In this study, first results were obtained with -carbonyl hydroquinones as antiplatelet agents; we found that linking triphenylphosphonium cation to a bicyclic carbonyl hydroquinone moiety by a short alkyl chain significantly improved their antiplatelet effect by affecting the mitochondrial functioning. The mechanism of action involves uncoupling OXPHOS, which leads to an increase in mitochondrial ROS production and a decrease in the mitochondrial membrane potential and OCR. This alteration disrupts the energy production by mitochondrial function necessary for the platelet activation process. These effects are responsive to the complete structure of the compounds and not to isolated parts of the compounds tested. The results obtained in this research can be used as the basis for developing new antiplatelet agents that target mitochondria.

中文翻译：

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将三苯基膦阳离子与双环氢醌连接通过调节线粒体功能提高其抗血小板作用


血小板是预防和治疗病理性血栓形成的关键靶点。然而，尽管目前采用抗血小板治疗，心血管死亡率仍然很高，并且处方患者中心血管事件仍在继续。在这项研究中，第一个结果是使用α-羰基氢醌作为抗血小板药物；我们发现，通过短烷基链将三苯基鏻阳离子连接到双环羰基氢醌部分，通过影响线粒体功能显着提高其抗血小板作用。作用机制涉及解偶联 OXPHOS，从而导致线粒体 ROS 产量增加，线粒体膜电位和 OCR 降低。这种改变破坏了血小板活化过程所需的线粒体功能的能量产生。这些效应与化合物的完整结构有关，而不是与测试化合物的孤立部分有关。本研究获得的结果可作为开发针对线粒体的新型抗血小板药物的基础。