Dutra Luiz Antonio, Guanaes Jéssica Frade O, Johmann Nadine, Lopes Pires Maria Elisa, Chin Chung Man, Marcondes Sisi, Dos Santos Jean Leandro
São Paulo State University (UNESP), School of Pharmaceutical Sciences, Araraquara, São Paulo, Brazil.
University of Campinas (Unicamp), Faculty of Medical Science, Campinas, SP, Brazil.
Bioorg Med Chem Lett. 2017 Jun 1;27(11):2450-2453. doi: 10.1016/j.bmcl.2017.04.007. Epub 2017 Apr 4.
Resveratrol (RVT) is a stilbene with a protective effect on the cardiovascular system; however, drawbacks including low bioavailability and fast metabolism limit its efficacy. In this work we described new resveratrol derivatives with nitric oxide (NO) release properties, ability to inhibit platelet aggregation and in vivo antithrombotic effect. Compounds (4a-f) were able to release NO in vitro, at levels ranging from 24.1% to 27.4%. All compounds (2a-f and 4a-f) have exhibited platelet aggregation inhibition using as agonists ADP, collagen and arachidonic acid. The most active compound (4f) showed reduced bleeding time compared to acetylsalicylic acid (ASA) and protected up to 80% against in vivo thromboembolic events. These findings suggest that hybrid resveratrol-furoxan (4f) is a novel lead compound able to prevent platelet aggregation and thromboembolic events.
白藜芦醇（RVT）是一种对心血管系统具有保护作用的芪类化合物；然而，包括低生物利用度和快速代谢在内的缺点限制了其疗效。在这项工作中，我们描述了具有一氧化氮（NO）释放特性、抑制血小板聚集能力和体内抗血栓作用的新型白藜芦醇衍生物。化合物（4a - f）能够在体外释放NO，释放水平在24.1%至27.4%之间。所有化合物（2a - f和4a - f）使用ADP、胶原蛋白和花生四烯酸作为激动剂时均表现出对血小板聚集的抑制作用。与阿司匹林（ASA）相比，活性最高的化合物（4f）显示出出血时间缩短，并且对体内血栓栓塞事件的保护作用高达80%。这些发现表明，白藜芦醇 - 呋咱杂化物（4f）是一种能够预防血小板聚集和血栓栓塞事件的新型先导化合物。
