高等学校化学学报 ›› 2018, Vol. 39 ›› Issue (10): 2198.doi: 10.7503/cjcu20180270

• 有机化学 • 上一篇    下一篇

硫辛酸酯类衍生物的合成及生物活性

张露云1,2, 徐倩2,3, 夏广清1,2, 丛丽2, 王雨2, 张辉1, 朱俊义2(), 臧皓2,3()   

  1. 1. 长春中医药大学吉林省人参科学研究院, 长春 130117
    2. 通化师范学院医药学院, 绿色药物化学实验室, 通化 134002
    3. 延边大学药学院, 延吉 133000
  • 收稿日期:2018-04-09 出版日期:2018-10-10 发布日期:2018-09-10
  • 作者简介:联系人简介: 臧 皓, 男, 博士, 副教授, 主要从事药物化学方面的研究. E-mail: zanghao_1984@163.com;朱俊义, 男, 博士, 教授, 主要从事生物活性方面的研究. E-mail: swx0527@163.com
  • 基金资助:
    吉林省科技发展计划项目(批准号: 20160520044JH)和吉林省中医药管理局科技项目(批准号: 2017110)资助.

Synthesis and Biological Activity of Lipoic Acid Ester Derivatives

ZHANG Luyun1,2, XU Qian2,3, XIA Guangqing1,2, CONG Li2, WANG Yu2, ZHANG Hui1, ZHU Junyi2,*(), ZANG Hao2,3,*()   

  1. 1. Jilin Ginseng Academy, Changchun University of Traditional Chinese Medicine, Changchun 130117, China
    2. School of Medicine, Green Medicinal Chemistry Laboratory, Tonghua Normal University, Tonghua 134002, China
    3. College of Medicine, Yanbian University, Yanji 133000, China
  • Received:2018-04-09 Online:2018-10-10 Published:2018-09-10
  • Contact: ZHU Junyi,ZANG Hao E-mail:swx0527@163.com;E-mail: zanghao_1984@163.com
  • Supported by:
    † Supported by the Fund of Science and Technology Development of Jilin Province, China(No.20160520044JH) and the Science and Technology Projects of Administration of Traditional Chinese Medicine of Jilin Province, China(No.2017110).

摘要:

以硫辛酸为原料, 对其羧基进行结构修饰, 合成了23个硫辛酸衍生物. 目标化合物的结构经核磁共振波谱和高分辨质谱分析确证. 生物活性测试结果表明, 在实验浓度下, 大部分化合物表现出一定的清除丙烯醛活性, 化合物3a, 3b, 3e, 3f, 3k, 3m, 3q, 3v和3w具有良好的清除丙烯醛活性, 其中化合物3a的清除活性高于对照品肌肽; 大部分化合物表现出一定的清除1,1-二苯基-2-三硝基苯肼(DPPH)活性, 化合物3o, 3p, 3v和3w具有良好的清除活性, 其中化合物3w的清除活性接近于对照品喹诺二甲基丙烯酸酯(Trolox)和维生素C; 大部分化合物表现出一定的2,2'-联氮双(3-乙基苯并噻唑啉-6-磺酸)二铵盐(ABTS)清除活性, 化合物3b, 3e, 3u, 3v和3w具有良好的清除活性, 其中化合物3w的清除活性非常接近于对照品Trolox和维生素C; 大部分化合物对铁离子-2,4,6-三(2-吡啶基)三嗪(Fe3+-TPTZ)复合物表现出一定的还原能力, 化合物3b, 3v和3w具有良好的还原能力, 其中化合物3w的还原能力高于对照品维生素C和Trolox; 大部分化合物表现出一定的清除羟基自由基活性, 化合物3j和3w具有良好的清除活性, 其中化合物3w的清除活性高于对照品Trolox. 血浆稳定性实验结果表明, 与硫辛酸相比, 23种化合物均具有很好的血浆稳定性.

关键词: 硫辛酸衍生物, 丙烯醛清除, 抗氧化活性, 血浆稳定性

Abstract:

A series of lipoic acid derivatives was synthesized via the modification of carboxyl groups of lipoic acid, 23 target compounds were obtained and characterized by nuclear magnetic resonance and high resolution mass spectrometry. Lipoic acid derivatives were employed in order to explore the potential structure-antioxidant activity relationships. The antioxidant activities of these compounds were evaluated and compared by the acrolein assay, 1,1-diphenyl-2-picrylhydrazyl(DPPH) assay, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium(ABTS) assay and ferric reducing antioxidant power(FRAP) assay. Acrolein scavenging activity test results showed that most compounds exhibited acrolein scavenging activities, compounds 3a, 3b, 3e, 3f, 3k, 3m, 3q, 3v and 3w had good acrolein scavenging activities, especially compound 3a showed the highest acrolein scavenging activity which was stronger than carnosine. The experimental results showed that most compounds exhibited DPPH scavenging activities, compounds 3o, 3p, 3v and 3w had good DPPH scavenging activities, especially compound 3w showed the highest DPPH scavenging activity, which was close to 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid(Trolox) and Vitamin C. The results showed that most compounds exhibited ABTS scavenging activities, compounds 3b, 3e, 3u, 3v and 3w had good ABTS scavenging activities, especially compound 3w showed the highest ABTS scavenging activity, which was very close to trolox and Vitamin C. FRAP experimental results showed that most compounds exhibited reduction activities to ferric ion-2,4,6-tri(2-pyridyl)-s-triazine(Fe3+-TPTZ) complex, compounds 3b, 3v and 3w had good reduction activities to Fe3+-TPTZ complex, especially compound 3w showed the highest reduction activity to Fe3+-TPTZ complex, which was stronger than Vitamin C and trolox. The results showed that most compounds exhibited hydroxyl radical scavenging activities, compounds 3j and 3w had good hydroxyl radical scavenging activities, especially compound 3w showed the highest hydroxyl radical scavenging activity which was stronger than trolox. Plasma stability assay results showed that compared with lipoic acid, twenty-three compounds had good plasma stability.

Key words: Lipoic acid derivative, Acrolein scavenging, Antioxidant activity, Plasma stability

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