Du Fangyu, Zhou Qifan, Fu Xiaoxiao, Shi Yajie, Chen Yuanguang, Fang Wuhong, Yang Jingyu, Chen Guoliang
Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University Shenyang 110016 P. R. China
Department of Pharmacology, Shenyang Pharmaceutical University Shenyang 110016 P. R. China
RSC Adv. 2019 Jan 21;9(5):2498-2508. doi: 10.1039/c8ra10424g. eCollection 2019 Jan 18.
The development of novel neuroprotection agents is of great significance for the treatment of ischemic stroke. In this study, a series of compounds comprising 2,2-dimethylbenzopyran groups and cinnamic acid groups have been synthesized. Preferential combination principles and bioisostere that improved the neuroprotective effect of the compounds were identified for this series biological activity assay . Meanwhile, a functional reversal group of the acrylamide amide resulted in the most active compounds. Among them, BN-07 significantly improved the morphology of neurons and obviously increased cell survival rate of primary neurons induced by oxygen glucose deprivation (OGD), superior to clinically used anti-ischemic stroke drug edaravone (Eda). Overall, our findings may provide an alternative strategy for the design of novel anti-ischemic stroke agents with more potency than Eda.
新型神经保护剂的开发对缺血性中风的治疗具有重要意义。在本研究中，合成了一系列包含2,2-二甲基苯并吡喃基团和肉桂酸基团的化合物。通过该系列生物活性测定，确定了提高化合物神经保护作用的优先结合原则和生物电子等排体。同时，丙烯酰胺酰胺的一个功能反转基团产生了活性最高的化合物。其中，BN-07显著改善了神经元的形态，并明显提高了氧糖剥夺（OGD）诱导的原代神经元的细胞存活率，优于临床使用的抗缺血性中风药物依达拉奉（Eda）。总体而言，我们的研究结果可能为设计比Eda更有效的新型抗缺血性中风药物提供一种替代策略。
