Department of Inorganic and Organic Chemistry, University of Jaén, Spain.
Bioorg Chem. 2010 Jun;38(3):108-14. doi: 10.1016/j.bioorg.2009.12.001. Epub 2009 Dec 5.
Polyphenols, such as rosmarinic acid, are widely distributed natural products with relevant antioxidant activity. Oxidative stress plays an important role in the pathogenesis of a number of disorders. Here, we report on the synthesis and biological effects of the polyphenolic esters hydroxytyrosyl gallate (1), hydroxytyrosyl protocatechuate (2) and hydroxytyrosyl caffeate (3), structurally related to rosmarinic acid. The three compounds showed a greater free radical scavenging activity than their precursors and also than rosmarinic acid. Esters 1 and 3 significantly reduced thrombin-evoked platelet aggregation, which is likely mediated to the attenuation of thrombin-stimulated Ca(2+) release and entry. The three compounds reduced the ability of platelets to accumulate Ca(2+) in the intracellular stores, probably by enhancing the Ca(2+) leakage rate and reduced store-operated Ca(2+) entry in these cells. These observations suggest that the structurally-simplified analogs to rosmarinic acid, compounds 1 and 3, might be the base of therapeutic strategies to prevent thrombotic complications associated to platelet hyperaggregability due to oxidative stress.
多酚，如迷迭香酸，是广泛分布的天然产物，具有相关的抗氧化活性。氧化应激在许多疾病的发病机制中起着重要作用。在这里，我们报告了多酚酯羟基酪醇没食子酸酯（1）、羟基酪醇原儿茶酸酯（2）和羟基酪醇咖啡酸酯（3）的合成及生物学效应，这些化合物与迷迭香酸在结构上有关。这三种化合物的自由基清除活性比其前体和迷迭香酸更强。酯 1 和 3 可显著抑制凝血酶诱导的血小板聚集，这可能是通过减弱凝血酶刺激的 Ca(2+)释放和内流来介导的。这三种化合物降低了血小板在细胞内储存中积累 Ca(2+)的能力，可能是通过增强 Ca(2+)泄漏率和减少这些细胞中储存操作的 Ca(2+)内流。这些观察结果表明，迷迭香酸的结构简化类似物，化合物 1 和 3，可能是预防与氧化应激引起的血小板高聚集性相关的血栓并发症的治疗策略的基础。
