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硫化氢供体型ADT-OH衍生物的合成及其活性

李玉姚, 宋恒, 程坚, 敖桂珍

李玉姚, 宋恒, 程坚, 敖桂珍. 硫化氢供体型ADT-OH衍生物的合成及其活性[J]. 中国药科大学学报, 2017, 48(3): 276-281. DOI: 10.11665/j.issn.1000-5048.20170304
引用本文: 李玉姚, 宋恒, 程坚, 敖桂珍. 硫化氢供体型ADT-OH衍生物的合成及其活性[J]. 中国药科大学学报, 2017, 48(3): 276-281. DOI: 10.11665/j.issn.1000-5048.20170304
LI Yuyao, SONG Heng, CHENG Jian, AO Guizhen. Synthesis and biological evaluation of H2S donor ADT-OH derivatives[J]. Journal of China Pharmaceutical University, 2017, 48(3): 276-281. DOI: 10.11665/j.issn.1000-5048.20170304
Citation: LI Yuyao, SONG Heng, CHENG Jian, AO Guizhen. Synthesis and biological evaluation of H2S donor ADT-OH derivatives[J]. Journal of China Pharmaceutical University, 2017, 48(3): 276-281. DOI: 10.11665/j.issn.1000-5048.20170304

硫化氢供体型ADT-OH衍生物的合成及其活性

基金项目: 苏州市科技计划资助项目(No.N313202713)

Synthesis and biological evaluation of H2S donor ADT-OH derivatives

  • 摘要: 二硫杂环化合物5-对羟基苯基-3H-1,2-二硫杂环戊烯-3-硫酮(ADT-OH)是一种缓释硫化氢供体,并具有一定的神经保护作用。为了研究其构效关系,对其芳环进行改造,合成了17个 Y 类化合物( Y1 ~ Y17),其结构均经 1H NMR、13C NMR 和HR-MS确证,其中6个化合物( Y4,Y13 ~ Y17 )结构是全新的。采用MTT法评价了该类化合物对谷氨酸诱导损伤的HT-22海马神经元细胞生存率的影响,结果发现,这些化合物在1~100 μmol/L浓度范围内具有很强的神经保护作用,其中化合物 Y1 ~ Y9,Y11 在全部测试浓度内均能非常显著地提高受损神经元的生存率(P<0.01),特别是化合物 Y1,Y4,Y6 ~ Y9,Y11 在1~10 μmol/L浓度范围内活性比ADT-OH强,值得进一步研究。
    Abstract: 5-(4-Hydroxyphenyl)-3H-1, 2-dithiole-3-thione(ADT-OH)is a slowly releasing H2S donor with some neuroprotective effect. In order to study the structure-activity relationships, seventeen compounds( Y1 - Y17 )were synthesized by modification of ADT-OH at the aromatic ring position, and their structures were confirmed by 1H NMR, 13C NMR and HR-MS. Among them, 6 compounds( Y4, Y13 - Y17 )were novel compounds. Their effects had been evaluated on HT-22 hippocampal neuron cells damaged by glutamate with MTT method. The pharmacological results demonstrated that all the Y compounds had potent neuroprotection at most of the tested concentrations(1-100 μmol/L). Compounds Y1 - Y9 and Y11 significantly improved the survival rates of the damaged cells at 1-100 μmol/L(P<0. 01). Specially, compounds Y1, Y4, Y6 - Y9, Y11 are more potent than their parent compound ADT-OH at concentration of 1-10 μmol/L, which is worthy of further study.
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出版历程
  • 刊出日期:  2017-06-24

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