Departamento de Física e Química, Faculdade de Engenharia de Ilha Solteira, Unesp- Univ Estadual Paulista, Ilha Solteira, São Paulo, Brazil.
Centro Universitário UNIFUNEC, Faculdade de Medicina, Santa Fé do Sul, São Paulo, Brazil.
Nat Prod Res. 2023 Jul;37(13):2198-2204. doi: 10.1080/14786419.2022.2036145. Epub 2022 Feb 5.
Total synthesis of taiwanin C was realised efficiently in a global yield of 52%. Taiwanin C in aggregation assays inhibited platelet aggregation in a concentration-dependent manner with an IC of 0.46 μM after exposure of human platelet to AA. Similarly, to AA, taiwanin C inhibited significantly TRAP-6-induced platelet aggregation with IC of 0.56 μM. Molecular docking studies were carried out using the molecular target the COX-1, COX-2 and PAR-1 proteins. These studies suggest that taiwanin inhibits COX-1 more strongly than COX-2. Taiwanin C showed better antiplatelet action in the presence of TRAP-6 than indomethacin and molecular docking studies suggest different mechanisms of action for the two compounds on PAR-1. These results demonstrate that taiwanin C acts very efficiently in two different signaling pathways of platelet aggregation. Although preliminary, these results indicate that taiwanin C has potential for further studies on its use for the development of new antiplatelet.
台湾 C 的全合成以全球产率 52%高效实现。在 AA 暴露于人血小板后，台湾 C 在聚集测定中以浓度依赖性方式抑制血小板聚集，IC 为 0.46 μM。同样，与 AA 相似，台湾 C 显著抑制 TRAP-6 诱导的血小板聚集，IC 为 0.56 μM。使用分子靶标 COX-1、COX-2 和 PAR-1 蛋白进行了分子对接研究。这些研究表明，台湾 C 对 COX-1 的抑制作用强于 COX-2。在 TRAP-6 存在下，台湾 C 显示出比吲哚美辛更好的抗血小板作用，分子对接研究表明这两种化合物对 PAR-1 的作用机制不同。这些结果表明，台湾 C 在血小板聚集的两种不同信号通路中非常有效。尽管初步研究结果表明，台湾 C 具有进一步研究其用于开发新型抗血小板药物的潜力。
