用于缺血性中风的黄芩素与川芎嗪活性代谢产物的杂合分子。
Hybrid molecules of scutellarein and tertramethylpyrazine's active metabolites for ischemic stroke.
作者信息
Dong Yongxi, Zhang Xiaohe, Liu Mingji, Yang Yang, Guo Ting, Mao Yuanhu, Zhang Jiquan, Fu Xiaozhong, Zhao Yonglong, Chen Jinglei, Dong Li, Qiao Chunhua
机构信息
College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China; School of Pharmacy, Guizhou Medical University, Guiyang 550025, China; Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guiyang 550004, China.
The 940th Hospital of Joint Logistics Support Force, Lanzhou 730050, China.
出版信息
Bioorg Med Chem Lett. 2019 Oct 1;29(19):126608. doi: 10.1016/j.bmcl.2019.08.012. Epub 2019 Aug 8.
A series of hybrid molecules of scutellarein and tertramethylpyrazine's active metabolites have been synthesized. Compared to the original compound, these prepared compounds exhibited higher water solubility, more appropriate logP and better stability. Importantly, compounds 11b, 11d and 11e showed improved neuroprotective activity against the HO-induced cell death in PC12 cells, and better antithrombosis activity. The optimized compound 11b was further evaluated by cerebral ischemia/ reperfusion in the middle cerebral artery occlusion (MCAO) model, the results showed that the compound could significantly reduce the infarct area and decrease the neuronal cell damage in CA1 pyramidal neurons. Overall, we demonstrated that the twin drug strategy could be applied in the development of agents for the treatment of ischemic stroke.
已经合成了一系列黄芩素和四甲基吡嗪活性代谢物的杂合分子。与原始化合物相比，这些制备的化合物表现出更高的水溶性、更合适的脂水分配系数（logP）和更好的稳定性。重要的是，化合物11b、11d和11e对HO诱导的PC12细胞死亡表现出改善的神经保护活性，以及更好的抗血栓形成活性。通过大脑中动脉闭塞（MCAO）模型中的脑缺血/再灌注对优化后的化合物11b进行了进一步评估，结果表明该化合物可显著减少梗死面积，并减少CA1锥体神经元中的神经元细胞损伤。总体而言，我们证明了双药策略可应用于缺血性中风治疗药物的开发。
Zotero 插件