金刚烷胺衍生物的合成和生物活性  

Synthesis and neuroprotective activity in cell culture of aminoadamantane analogues

作　　者：李艳萍[1] 李卓荣[1] 曹珏[1] 陶玉杰[1] 

机构地区：[1]中国医学科学院中国协和医科大学医药生物技术研究所,北京100050

出　　处：《药学学报》2007年第4期392-395,共4页Acta Pharmaceutica Sinica

摘　　要：为了寻找新的神经元保护剂,合成了7个新的1位氮取代的金刚烷胺类衍生物,其结构均经核磁共振氢谱(1H NMR)、MS-FAB和高分辨质谱(HRMS)确证;以四甲基偶氮唑盐(MTT)微量比色法和乳酸脱氢酶(LDH)漏出率测定法初步考察了所合成化合物体外对谷氨酸损伤神经细胞的保护作用,研究显示,500μmol.L-1谷氨酸能够引起神经元细胞发生明显的损伤性变化,细胞死亡率升高,MTT值明显降低,LDH漏出率增加;加入一定浓度的化合物能够显著提高谷氨酸损伤的人神经母细胞瘤株SY5Y的MTT代谢率,降低细胞死亡率,而且进一步研究显示化合物3d和4 c能显著降低LDH漏出率,对谷氨酸损伤的神经细胞体外模型显示了保护作用。Seven novel derivatives of aminoadamantane with 1-aminosubstituted group were synthesized from amantadine or memantine individually in order to find new neuroprotective agent. Six of them are amides of two precursors, one is a 1-amino derivative of memantine substituted with 2-hydroxy propyl. Their chemical structures were confirmed by ^1H NMR and HRMS. The neuroprotective activity in vitro was evaluated primarily with 500 μmol · L^-1 glutamate damaged SY5Y cell by measurement of MTT metabolic rate and LDH leakage rate. Glutamate reduced MTT metabolic rate, but increased LDH leakage rate significantly. The addition of new derivatives elevated the MTT value with their certain concentration, reduced cell death rate. Especially as for 3d and 4c, they fully normalized LDH leakage rate with concentration of 20 μmol · L^-1 during LDH measurement. These data indicated that 3d and 4c have significant protective effect on nerve cell against glutamate injury, deserved to be further tested and maybe helpful for treatment of neurodegenerative disease.

关 键 词：金刚烷胺 美金刚胺 衍生物 谷氨酸 

分 类 号：R916.2[医药卫生—药学]