摘要
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。
Ligustrazine,one of the major effective components of the Chinese traditional medicinal herb Ligusticum Chuanxiong Hort,has been reported plenty of biological activities,such as protect cardiovascular and cerebrovascular,neuroprotection and anti-tumor,et al. Because of its remarkable effects,studies on structural modification of ligustrazine have attracted much attention. Ligustrazine synthetic derivatives reported in recent decades are mainly derived from four primary intermediates（ TMP-COOH,TMP-OH,TMP-NH2,HO-TMP-OH）. To explore the neuroprotection activitiy of ligustrazine intermediates,six ligustrazine intermediates（ 2,5,8,11,12,13） were synthesized and their protective effects against CoCl2-induced neurotoxicity in differentiated PC12 cells were studied. The target compounds were prepared via different chemical methods,including oxidation,substitution,esterification and amidation without changing the structure nucleus of ligustrazine. Compared with TMP（ EC50= 56. 03 μmol·L-1）,four compounds（ 2,5,12and 13） exhibited higher activity（ EC50 50 μmol·L-1） respectively,of which,compound 2 displayed the highest protective effect against the damaged PC12 cells（ EC50= 32. 86 μmol·L-1）,but target compounds8 and11 appeared lower activity（ EC50 〉70 μmol·L-1）. By structure-activity relationships analysis,the introduction of carboxyl,amino to the side chain of ligustrazine and appropriately increase the proportion of ligustrazine may contribute to enhance its neuroprotective activity,which provides a reference for the design,synthesis and activity screening of relevant series of ligustrazine derivatives in the future.
出处
《中国中药杂志》
CAS
CSCD
北大核心
2014年第14期2679-2683,共5页
China Journal of Chinese Materia Medica
基金
国家自然科学基金项目(81173519)
北京中医药大学创新团队项目(2011-CXTD-15)
关键词
川芎嗪中间体
PC12细胞
神经保护
构效关系
ligustrazine intermediates
PC12 cell
neuroprotection
structure-activity relationships
