氮氧自由基与γ-氨基丁酸偶联物的设计合成与抗缺氧活性研究  

A Study on Design,Synthesis and Anti-hypoxia Activity of Nitronyl Nitroxide-γ-aminobutyric Acid Conjugate

作　　者：景临林[1] 马慧萍[1] 樊鹏程[1] 何蕾[1] 贾正平[1] 

机构地区：[1]兰州军区兰州总医院药剂科全军高原损伤防治重点实验室,兰州730050

出　　处：《解放军医药杂志》2015年第12期1-4,20,共5页Medical & Pharmaceutical Journal of Chinese People’s Liberation Army

基　　金：国家自然科学基金项目(81202458);全军医药科研"十二五"面上项目(CLZ12JA04);甘肃省自然科学基金(1308RJYA06);中国博士后科学基金(2012M521926)

摘　　要：目的设计合成一种新型氮氧自由基与γ-氨基丁酸偶联物并研究其抗缺氧活性。方法以对羟基苯甲醛、溴乙酸乙酯、γ-氨基丁酸甲酯盐酸盐和2,3-二甲基-2,3-二羟氨基丁烷为原料,经醚化、酰胺化、缩合和氧化反应得到一种氮氧自由基与γ-氨基丁酸的偶联物(化合物3),并通过小鼠常压密闭耐缺氧实验对其抗缺氧活性进行评价。结果 3组在常压密闭缺氧实验下,与缺氧模型组比较,乙酰唑胺组和化合物3组存活时间均明显延长,差异有统计学意义(P<0.01),化合物3组与乙酰唑胺组比较存活时间延长(P<0.01)。与正常对照组比较,缺氧模型组中LD含量显著升高(P<0.01),LDH活性显著降低(P<0.01);与缺氧模型组比较,化合物3组小鼠血浆中LD含量差异无统计学意义,但是LD累积速率明显降低,差异有统计学意义(P<0.01)。结论氮氧自由基与γ-氨基丁酸偶联物的设计路线合理,合成方法简便,产率较高,并且表现出了较高的抗缺氧活性。Objective To design the synthesis of a nitronyl nitroxide-γ-aminobutyric acid conjugate and to investigate its anti-hypoxia activity. Methods A nitronyl nitroxide-γ-aminobutyric acid conjugate（ compound 3） was achieved via etherification,amidation,condensation and oxidizing reaction using 4-hydroxybenzaldehyde,ethyl bromoacetate,methyl 4-aminobutyrate hydrochloride and 2,3-dimethyl-2,3-dihydroxylamino butane as starting materials. The anti-hypoxic activities of the compound were evaluated using the normobaric hypoxia experiment of mice. Results Compared with those in the hypoxia model group,Acetazolamide and compound 3 groups had significantly prolonged survival time in the three groups under normobaric hypoxia experiment,and the differences were statistically significant（ P〈0. 01）. The survival time of mice in compound 3 group was significantly longer than that in Acetazolamide group（ P〈0. 01）. Compared with those in the normal control group,the lactic acid（ LD） content was significantly increased,while the l-lactate dehydrogenase（ LDH） activity was significantly decreased in compound 3 group（ P〈0. 01）. Compared with those in the hypoxia model group,the LD content had no significant changes,but the LD accumulation rate was significantly decreased in compound 3 group（ P〈0. 01）. Conclusion The synthetic route of the nitronyl nitroxide-γ-aminobutyric acid conjugate is rational and simple with high yield,and it exhibits excellent anti-hypoxic activity.

关 键 词：氮氧自由基 Γ-氨基丁酸 设计合成 抗缺氧活性 

分 类 号：R34[医药卫生—基础医学]