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硫化氢供体型美金刚衍生物的合成及其活性

孙银星, 吴颖, 宋恒, 程坚, 敖桂珍

孙银星, 吴颖, 宋恒, 程坚, 敖桂珍. 硫化氢供体型美金刚衍生物的合成及其活性[J]. 中国药科大学学报, 2016, 47(5): 543-547. DOI: 10.11665/j.issn.1000-5048.20160506
引用本文: 孙银星, 吴颖, 宋恒, 程坚, 敖桂珍. 硫化氢供体型美金刚衍生物的合成及其活性[J]. 中国药科大学学报, 2016, 47(5): 543-547. DOI: 10.11665/j.issn.1000-5048.20160506
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SUN Yinxing, WU Ying, SONG Heng, CHENG Jian, AO Guizhen. Synthesis and biological evaluation of H2S donor memantine derivatives[J]. Journal of China Pharmaceutical University, 2016, 47(5): 543-547. DOI: 10.11665/j.issn.1000-5048.20160506
Citation: SUN Yinxing, WU Ying, SONG Heng, CHENG Jian, AO Guizhen. Synthesis and biological evaluation of H2S donor memantine derivatives[J]. Journal of China Pharmaceutical University, 2016, 47(5): 543-547. DOI: 10.11665/j.issn.1000-5048.20160506
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硫化氢供体型美金刚衍生物的合成及其活性

  • 1.

    苏州大学药学院

  • 2.

    苏州大学神经科学研究所

基金项目: 苏州市科技计划资助项目(No.N313202713)

Synthesis and biological evaluation of H2S donor memantine derivatives

摘要

    摘要
  • 摘要: H2S具有保护缺血再灌注损伤的神经元、显著降低脑梗死面积的作用，但高浓度H2S产生神经毒性。N-甲基-D-天冬氨酸(NMDA)受体拮抗剂美金刚可以降低高浓度H2S引起的神经毒性。将硫化氢缓释供体5-对羟基苯基-1，2-二硫杂环戊烯-3-硫酮(ADT-OH)与美金刚通过烷烃连接臂拼合，设计了9个结构全新的化合物 I 1~ I 9 ，以ADT-OH为原料，经过4步反应得到目标化合物，其化学结构经1H NMR、13C NMR和HRMS确证。利用MTT法评价不同浓度目标化合物对谷氨酸损伤的HT-22细胞的影响，结果发现，该类化合物在1 μmol/L时能明显提高受损HT-22细胞的生存率(P<；0.01)，对于谷氨酸诱导损伤的神经元细胞具有较好的保护作用。
    Abstract: H2S has a role of protecting neurons from ischemia-reperfusion injury and significantly reducing the cerebral infarction area, but high concentration of H2S can induce neurotoxicity. Memantine, a N-methyl-D-aspartic acid(NMDA)receptor antagonist, could reduce the neurotoxicity of H2S at high concentration. Nine novel structures(compounds I 1- I 9)were designed by coupling(4-hydroxy phenyl)-3H-1, 2-dithiole-3-thione(ADT-OH)with memantine through alkanes as linkers and synthesized by four-step reactions from ADT-OH. Their neuroprotection against damage induced by glutamate on HT-22 cells was evaluated by MTT method. The results indicated that these compounds markedly increased the survival rates of damaged HT-22 cells at the concentration of 1 μmol/L(P< 0. 01), which suggested that these compounds could preferably protect neurons against damage induced by glutamate.
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    • 参考文献(12)
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  • 刊出日期:  2016-10-24

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