School of Pharmacy, University of Reading, Reading, UK.
School of Pharmacy, University of Reading Malaysia, Johor, Malaysia.
Sci Rep. 2018 Jun 22;8(1):9528. doi: 10.1038/s41598-018-27809-z.
Flavonoids exert innumerable beneficial effects on cardiovascular health including the reduction of platelet activation, and thereby, thrombosis. Hence, flavonoids are deemed to be a molecular template for the design of novel therapeutic agents for various diseases including thrombotic conditions. However, the structure-activity relationships of flavonoids with platelets is not fully understood. Therefore, this study aims to advance the current knowledge on structure-activity relationships of flavonoids through a systematic analysis of structurally-related flavones. Here, we investigated a panel of 16 synthetic flavones containing hydroxy or methoxy groups at C-7,8 positions on the A-ring, with a phenyl group or its bioisosteres as the B-ring, along with their thio analogues possessing a sulfur molecule at the 4 carbon position of the C-ring. The antiplatelet efficacies of these compounds were analysed using human isolated platelets upon activation with cross-linked collagen-related peptide by optical aggregometry. The results demonstrate that the hydroxyl groups in flavonoids are important for optimum platelet inhibitory activities. In addition, the 4-C=O and B ring phenyl groups are less critical for the antiplatelet activity of these flavonoids. This structure-activity relationship of flavonoids with the modulation of platelet function may guide the design, optimisation and development of flavonoid scaffolds as antiplatelet agents.
类黄酮对心血管健康有无数有益的影响，包括减少血小板的激活，从而防止血栓形成。因此，类黄酮被认为是设计新型治疗各种疾病（包括血栓形成）药物的分子模板。然而，类黄酮与血小板的结构-活性关系尚未完全阐明。因此，本研究旨在通过对结构相关的黄酮类化合物进行系统分析，推进类黄酮结构-活性关系的现有知识。在这里，我们研究了一组 16 种合成黄酮类化合物，它们在 A 环的 C-7、8 位上含有羟基或甲氧基，B 环上有苯基或其生物等排体，以及它们的 C-环 4 位上含有硫原子的硫类似物。通过光学聚集仪分析用交联胶原相关肽激活的人分离血小板，研究了这些化合物的抗血小板功效。结果表明，黄酮类化合物中的羟基对于最佳的血小板抑制活性很重要。此外，4-C=O 和 B 环上的苯基对于这些黄酮类化合物的抗血小板活性不太关键。类黄酮与血小板功能调节的这种结构-活性关系可能为设计、优化和开发作为抗血小板剂的类黄酮支架提供指导。
