全部 标题 作者
关键词 摘要

OALib Journal期刊
ISSN: 2333-9721
费用:99美元

查看量下载量

相关文章

更多...

川芎嗪中间体的合成及其对CoCl2致分化PC12细胞损伤的保护作用

Keywords: 川芎嗪中间体,PC12细胞,神经保护,构效关系

Full-Text   Cite this paper   Add to My Lib

Abstract:

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。

References

[1]  王鹏龙, 徐昕, 李国梁, 等. 新型川芎嗪衍生物的合成及其抗癌活性研究[J]. 西北药学杂志, 2014, 29(1): 58.
[2]  Xu K, Wang P L, Xu X, et al. An overview on structural modifications of ligustrazine and biological evaluation of its synthetic derivatives[J]. Res Chem Intermediat, 2013, doi:10.1007/s11164-013-1281-2.
[3]  Wang P L, Cheng Y T, Xu K, et al. Synthesis and anti-tumor evaluation of one novel tetramethylpyrazine-rhein derivative[J]. Asian J Chem, 2013, 25(9): 4885.
[4]  Chen H F, Li G N, Zhan P, et al. Design, synthesis and biological evaluation of novel ligustrazinyloxy-cinnamic acid derivatives as potent cardiovascular agents[J]. Eur J Med Chem, 2011, 46: 5609.
[5]  Wang P L, Zhang Y Z, Xu K, et al. A new ligustrazine derivative-pharmacokinetic evaluation and antitumor activity by suppression of NF-κB/p65 and COX-2 expression in S180 mice[J]. Die pharmazie, 2013, 68(9): 782.
[6]  杨杰. 川芎嗪的结构修饰及生物活性实验研究.西安: 陕西师范大学, 2003.
[7]  王鹏龙, 程亚涛, 汪林, 等. 齐墩果酸和去氧胆酸衍生物合成及抗血管生成活性研究[J]. 首都医科大学学报, 2012, 33(4): 494.
[8]  绪扩, 王鹏龙, 汪林, 等. 四甲基吡嗪系列衍生物合成中间体的制备工艺研究进展[J]. 中国新药杂志, 2013, 22(9): 1038.
[9]  Vaudry D, Stork P J S, Lazarovici P, et al. Signaling pathways for PC12 cell differentiation: making the right connections [J]. Science, 2002, 5573 (296): 1648.
[10]  Klesse L J, Meyers K A, Marshall C J, et al. Nerve growth factor induces survival and differentiation through two distinct signaling cascades in PC12 cells[J]. Oncogene, 1999, 18(12): 2055.
[11]  陈学敏,许淑菊,马永雯. 2-羟甲基-3,5,6-三甲基吡嗪的合成及其对血液流变性的影响[J].中国药物化学杂志,1996,6(4): 254.
[12]  刘建建. 川芎嗪衍生物的设计、合成及其生物活性研究. 济南: 山东大学, 2006.
[13]  陈欣,董善年.川芎嗪在兔体内代谢产物的研究[J].药学学报,1996,31(8): 617.
[14]  刘新泳,葛蔚颖,徐丽君,等.川芎嗪体内代谢产物的合成[J].山东医科大学学报,1997,35(1): 80.
[15]  Klein B, Berkowitz J. Pyrazines. I. Pyrazine-N-oxides. Preparation and spectral characteristics[J]. J Am Chem Soc, 1959, 81(19): 5160.
[16]  Fialho A M, Gupta T K D, Chakrabarty A M. Designing promiscuous drugs look at what nature made[J]. Lett Drug Des Discov, 2007, 4(1): 40.
[17]  刘珂.源于传统中药的先导化合物筛选与优化[J].中国医药技术经济与管理,2007,1(4): 62.
[18]  Li Z Y, Yu F, Cui L, et al. Design, synthesis and evaluation of novel ligustrazinyl acylguanidine derivatives as potential cardiovascular agents[J]. Med Chem, 2012, 8(5):928.
[19]  Wang P L, Zhang H G, Chu F H, et al. Synthesis and protective effect of new ligustrazine-benzoic acid derivatives against CoCl2 induced neurotoxicity in differentiated PC12 cells[J]. Molecules, 2013, 18(10): 13027.
[20]  Wang P L, She G M, Yang Y N, et al. Synthesis and biological evaluation of new ligustrazine derivatives as anti-tumor agents[J]. Molecules, 2012, 17(5): 4972.

Full-Text

Contact Us

service@oalib.com

QQ:3279437679

WhatsApp +8615387084133