氮氧自由基与酪氨酸偶联物的设计合成与抗缺氧活性研究  

Design,synthesis and anti-hypoxia activity of conjugates of HPN and tyrosine linked by alkyl carbon chain

作　　者：张书瑜 达清越 马慧萍 景临林 ZHANG Shu-yu;DA Qing-yue;MA Hui-ping;JING Lin-li(Department of Pharmacy,The 940th Hospital of Joint Logistics Support Force of PLA,Lanzhou 730050,China;Department of Pharmacy,the First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061,China)

机构地区：[1]中国人民解放军联勤保障部队第九四〇医院药剂科,甘肃兰州730050 [2]西安交通大学第一附属医院药学部,陕西西安710061

出　　处：《化学研究与应用》2023年第11期2783-2787,共5页Chemical Research and Application

基　　金：国家自然科学基金项目(81872796)资助;西安交通大学第一附属医院科研发展基金项目(2022MS-11)资助。

摘　　要：为了提高氮氧自由基HPN的靶向性和抗缺氧活性,本研究基于大中型氨基酸转运体(LAT-1)在脑组织高表达的特点,将HPN同酪氨酸通过不同长度烷基链相连,设计合成了2个脑靶向HPN衍生物。化合物7、8产率均在60%以上,产物结构经红外光谱(IR)、电子顺磁共振(EPR)、高分辨质谱(HRMS)分析确认。抗缺氧活性实验结果表明:两个化合物可以延长常压密闭缺氧小鼠的生存时间,降低急性减压缺氧小鼠的死亡率,并且在仅为HPN给药剂量一半的情况下表现出与HPN相似的抗缺氧活性。In order to improve the brain targeting efficiency and anti-hypoxia activity of HPN,two brain targeted HPN derivatives were designed and synthesized by coupling of HPN with tyrosine via different long of alkyl carbon chain,based on the theory of the large amino acid transporter 1(LAT1)was high expressed at the brain tissue.Compounds 7 and 8 were produced in over 60%yield.The structures of these products were confirmed by infrared spectroscopy(IR),electron paramagnetic resonance(EPR)and high res-olution mass spectrometry(HRMS)analysis.The results of anti-hypoxia activities indicated that two compounds could prolong the survival time of mice and reduce the mortality of mice compared with the model group,and exhibited similar anti-hypoxia activity as HPN at the half dose of HPN.

关 键 词：氮氧自由基 酪氨酸 L型氨基酸转运体1 脑靶向 

分 类 号：O629.71[理学—有机化学]