张斌, 刘万冬, 李家明, 金凡, 钱诗虎. 丁苯酞衍生物的设计、合成及神经细胞保护和抗血小板聚集活性研究J. 药学学报, 2020,55(3): 478-483. doi: 10.16438/j.0513-4870.2019-0969
引用本文: 张斌, 刘万冬, 李家明, 金凡, 钱诗虎. 丁苯酞衍生物的设计、合成及神经细胞保护和抗血小板聚集活性研究J. 药学学报, 2020,55(3): 478-483. doi: 10.16438/j.0513-4870.2019-0969
ZHANG Bin, LIU Wan-dong, LI Jia-ming, JIN Fan, QIAN Shi-hu. Design, synthesis, and neuroprotective and anti-platelet aggregation research of 3-n-butylphthalide derivativesJ. Acta Pharmaceutica Sinica, 2020,55(3): 478-483. doi: 10.16438/j.0513-4870.2019-0969
Citation: ZHANG Bin, LIU Wan-dong, LI Jia-ming, JIN Fan, QIAN Shi-hu. Design, synthesis, and neuroprotective and anti-platelet aggregation research of 3-n-butylphthalide derivativesJ. Acta Pharmaceutica Sinica, 2020,55(3): 478-483. doi: 10.16438/j.0513-4870.2019-0969

丁苯酞衍生物的设计、合成及神经细胞保护和抗血小板聚集活性研究

Design, synthesis, and neuroprotective and anti-platelet aggregation research of 3-n-butylphthalide derivatives

  • 摘要: 丁苯酞与阿魏酸对缺血性脑卒中都具有较好治疗效果。本研究采用分子杂交策略,以苯甲酸为原料通过亲核取代、还原、酯化及消除反应合成12个丁苯酞衍生物,经1H NMR、13C NMR、ESI-MS确证其结构。首先,采用MTT法测试所有化合物对氧糖剥夺诱导大鼠脑皮层神经元损伤的体外保护活性。其次,采用Bron比浊法测定具有最好神经细胞保护活性化合物,对花生四烯酸及二磷酸腺苷的血小板聚集的抑制活性。结果表明,化合物7b不仅表现出强效的神经细胞保护活性,还具有良好的抗血小板聚集活性,存在研发成治疗缺血性脑卒中药物的潜力。

     

    Abstract: Butylphthalide and ferulic acid exhibit excellent therapeutic effects in ischemic stroke. In this research, twelve 3-n-butylphthalide derivatives were designed by molecular hybridization strategy. The target compounds were obtained by nucleophilic substitution, reduction reaction, esterification reaction and elimination reaction, and the structure was confirmed by 1H NMR, 13C NMR and ESI-MS. All compounds were evaluated for neuroprotective activity against OGD/R-induced neurotoxicity in rat cortical neurons by MTT assay. The compounds with the best neuroprotective activity were biologically evaluated for their ability to inhibit platelet aggregation induced by arachidonic acid (AA) and adenosine diphosphate (ADP) via the Bron method.The results indicate that 7b exhibited potent neurocyte protective activity as well as prominent anti-platelet aggregation activity. Compound 7b has potential to be developed as a drug for ischemic stroke.

     

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