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该研究通过氧化、取代、酯化、酰胺化等方法改变川芎嗪侧链结构,合成川芎嗪中间体6个,并采用CoCl2致PC12细胞损伤模型,评价中间体的神经保护作用。研究显示,在川芎嗪侧链引入功能基团的中间体2,5,12和13对CoCl2损伤的PC12细胞具有较好的保护作用,其保护作用均明显强于原料药川芎嗪。经构效关系分析,川芎嗪侧链引入羧基、氨基和适当增加川芎嗪单元比重可能有助于增强此类结构的神经保护活性,该研究为设计合成具有神经保护活性的川芎嗪系列衍生物提供参考。
In this study, 6 tetramethylpyrazine intermediates were synthesized by changing the side chain of tetramethylpyrazine by means of oxidation, substitution, esterification and amidation. The injury model of PC12 cells induced by CoCl2 was used to evaluate the neuroprotective effects of intermediates. The results showed that intermediates 2, 5, 12, and 13 with functional groups introduced into tetramethylpyrazine side chains have good protective effects on PC12 cells damaged by CoCl2, and their protective effects are significantly stronger than that of ligustrazine. The structure-activity relationship analysis, tetramethylpyrazine side chain introduction of carboxyl, amino and appropriate increase tetramethylpyrazine unit specific gravity may help enhance the structure of neuroprotective activity, the study for the design and synthesis of neuroprotective tetramethylpyrazine derivatives provide reference.