Sheng Xiao, Hua Kai, Yang Chunyu, Wang Xiaoli, Ji Hui, Xu Jinyi, Huang Zhangjian, Zhang Yihua
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China; Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009, PR China; Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009, PR China; Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 201203, PR China.
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China; Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, PR China.
Bioorg Med Chem Lett. 2015 Sep 1;25(17):3535-40. doi: 10.1016/j.bmcl.2015.06.090. Epub 2015 Jul 3.
Fourteen hybrids (10a-g, 11a-g) of 3-n-butylphthalide (NBP) and edaravone (Eda) analogues have been designed and synthesized as potential anti-ischemic stroke agents. In vitro biological studies showed that compounds 10d and 10g exhibited more potent anti-platelet aggregation than ticlopidine (Ticlid), aspirin (ASP) and NBP. Compound 10g more significantly prevented H2O2-mediated neuronal cell (PC12) death than NBP, Eda or NBP together with Eda. Meanwhile, 10g also possessed potent radical scavenging effects on hydroxyl radical (˙OH) and superoxide anion radical (˙O2(-)). Our findings may provide new insights into the development of these hybrids, like 10g, for the intervention of ischemic stroke.
已设计并合成了14种3 - 正丁基苯酞（NBP）与依达拉奉（Eda）类似物的杂合物（10a - g，11a - g）作为潜在的抗缺血性中风药物。体外生物学研究表明，化合物10d和10g表现出比噻氯匹定（抵克立得）、阿司匹林（ASP）和NBP更强的抗血小板聚集作用。化合物10g比NBP、Eda或NBP与Eda联合使用更显著地预防了H2O2介导的神经元细胞（PC12）死亡。同时，10g对羟自由基（˙OH）和超氧阴离子自由基（˙O2(-)）也具有强大的自由基清除作用。我们的研究结果可能为开发像10g这样的杂合物用于干预缺血性中风提供新的见解。
