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有机化学
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有机化学 ›› 2010, Vol. 30 ›› Issue (05): 675-683. 上一篇    下一篇

研究论文

阿德福韦双L-氨基酸酯与葫芦脲的主客体化学与抗乙型肝炎病毒活性研究

傅晓钟*,1，黄英2，陶朱2，薛赛凤2，罗春1，欧瑜1，张建新3   

  1. (1贵阳医学院药学院 贵阳 550004)
    (2贵州大学理学院应用化学研究所 贵阳 550025)
    (3贵州省天然产物重点化学实验室 贵阳 550002)
  • 收稿日期:2009-06-29 修回日期:2009-11-10 发布日期:2009-12-14
  • 通讯作者: 傅晓钟 E-mail:xiaozhong_fu@sina.com
  • 基金资助:

    贵州省教育厅自然科学研究基金（黔教科2007033）资助项目

Investigation of Complex of Cucurbit[6, 7, 8]urils with Adefovir Bis(L-amino acid) Ester Prodrug and Its Anti-HBV Activity

Fu Xiaozhong*,1 Huang Ying2 Tao Zhu2 Xue Saifeng2 Luo Chun1, Ou Yu1 Zhang Jianxin3   

  1. (1 School of Pharmacy, Guiyang Medical College, Guiyang 550004)
    (2 Institute of Applied Chemistry, Guizhou University, Guiyang 550025)
    (3 Key Laboratory of Chemistry for Natural Products of Guizhou Province, Guiyang 550002)
  • Received:2009-06-29 Revised:2009-11-10 Published:2009-12-14
  • Contact: FU Xiao-Zhong E-mail:xiaozhong_fu@sina.com

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用1H NMR、荧光光谱和红外光谱方法研究阿德福韦双L-苯丙氨酸丙酯(FH-1)与改性六元葫芦脲(TMeQ[6])、七元葫芦脲(Q[7])以及八元葫芦脲(Q[8])的相互作用, 探讨主客体作用位点及其识别机制. 1H NMR图谱表明FH-1中苯丙氨酸残基部分进入葫芦脲的空腔内部受到屏蔽作用, 而FH-1其它部分则位于葫芦脲端口外侧. 荧光图谱表明FH-1与TMeQ[6], Q[7]与Q[8]分别形成1∶1或2∶1, 1∶1或3∶1与2∶1的主客体包结配合物. 红外光谱表明Q[7]与FH-1固体包合物发生了主客体相互作用, FH-1特征峰消失. 吸湿性考察发现FH-1与Q[7]形成的固体包合物的吸湿稳定性明显提高, 室温放置90 d后仍然为白色固体. 抗乙型肝炎病毒研究提示葫芦脲具有明显降低化合物细胞毒性, 增加其抗病毒活性与作用选择性的效果.

关键词: 阿德福韦, L-氨基酸, 葫芦脲, 主客体包结配合物

The interaction properties and mechanism of host-guest of cucurbit[6, 7, 8]urils with adefovir bis(L-phenylalanine propyl) ester prodrug have been investigated by 1H NMR technique, fluorescence spectrophotometry and IR spectroscopy. The experimental results revealed that cucurbit[n]urils can form host-guest complex with adefovir prodrug, and phenylalanine residue of guest FH-1 is located in the shielding zone of the cavity of Q[6, 7, 8], other parts of FH-1 is located at the deshielding portal of the host. Fluorometric analysis revealed that FH-1 can form inclusion complex with Q[6], Q[7], Q[8] with a ratio of 1∶1 or 2∶1, 1∶1 or 3∶1 and 2∶1, respectively. Hygroscopic stability studies indicated that moisture stability of host-guest complex is significantly enhanced. Anti-HBV study showed that host-guest complex significantly increases anti-HBV activity and selective index of the adefovir prodrug.

Key words: adefovir, L-amino acid, cucurbit[n]uril, host-guest complex