真空条件下青蒿素类药物的环糊精包结作用机制研究  

Mechanism of cyclodextrin inclusion of artemisinins in vacuum

作　　者：郭涛[1] 李海燕[1] 殷宪振[1] 郭桢[1,2] 张继稳[1] 

机构地区：[1]中国科学院上海药物研究所,上海201203 [2]浙江中医药大学,杭州310053

出　　处：《中国药科大学学报》2010年第6期513-519,共7页Journal of China Pharmaceutical University

基　　金：国际科技合作资助项目(No.S2010GR0920);国家"重大新药创制"科技重大专项资助项目(No.2009ZX09301-001);上海市科委资助项目(No.08DZ1980200;08431903100);中国科学院上海药物研究所知识创新工程青年人才领域前沿资助项目(No.SIMM0912QN-08)~~

摘　　要：研究真空中α-、β-和γ-环糊精对青蒿素类药物(双氢青蒿素、蒿甲醚、蒿乙醚和青蒿琥酯)的包结情况,从原子相互作用角度分析不同大小结合能产生的原因,为难溶性药物环糊精包结物的设计和早期评价提供理论基础。采用分子力学和分子动力学计算程序,考察摩尔比1:1时的各种包结情形,得到真空中每一种包结物的结合能。青蒿素类药物的环糊精包结物在真空中的相互作用力主要是氢键作用和范德华力,不同的结合方式导致了不同的结合能,青蒿素中过氧桥的存在可使包结物更稳定。To frame the molecular simulation foundation in early stage evaluation for the design and evaluation of the cyclodextrin inclusions for poorly soluble drugs,the inclusion cases of cyclodextrin（α-,β-and γ-cyclodextrin） to artemisinins（dihydroartemisinin,artesunate,artemether and arteether） in vacuum were studied and the mechanisms for the binding energy differences were analyzed in term of atomic interaction.The molecular mechanics and molecular dynamics programs were employed to calculate the inclusion cases of cyclodextrins to artemisinins at molar ratio of 1：1.The binding energy of each complex in vacuum was predicted.It was indicated that hydrogen bonding and van der Waals force are mainly attributed to the interaction force of cyclodextrin to artemisinin analogs in vacuum.Different interaction patterns resulted in varied binding energies.The peroxo bridges in the structure of artemisinin analogs may also play a role in stabilizing the inclusion complexes.

关 键 词：青蒿素 环糊精 分子模拟 结合能 氢键 

分 类 号：R283[医药卫生—中药学]