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  

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

作　　者：傅晓钟[1] 黄英[2] 陶朱[2] 薛赛凤[2] 罗春[1] 欧瑜[1] 张建新 

机构地区：[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

出　　处：《有机化学》2010年第5期675-683,共9页Chinese Journal of Organic Chemistry

基　　金：贵州省教育厅自然科学研究基金(No黔教科2007033)资助项目

摘　　要：用1HNMR、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.1HNMR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90d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.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 IH 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 shield- ing 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.

关 键 词：阿德福韦 L-氨基酸 葫芦脲 主客体包结配合物 

分 类 号：R91[医药卫生—药学] R96