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题名: Insight into the effects of chiral isomers quinidine and quinine on CYP2D6 inhibition
作者: Ai, Chunzhi1, 2;  Li, Yan3;  Wang, Yonghua4;  Chen, Yadong5;  Yang, Ling1, 2
关键词: Stereoisomer ;  CYP2D6 ;  Inhibitor ;  CoMFA ;  CoMSIA ;  Docking ;  Molecular electrostatic potential
刊名: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
发表日期: 2009-02-01
DOI: 10.1016/j.bmcl.2008.12.016
卷: 19, 期:3, 页:803-806
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology ;  Life Sciences & Biomedicine ;  Physical Sciences
类目[WOS]: Chemistry, Medicinal ;  Chemistry, Organic
研究领域[WOS]: Pharmacology & Pharmacy ;  Chemistry
英文摘要: The distinct inhibitory effects against CYP2D6 enzyme of the stereoisomers quinidine and quinine were investigated in this work by employing various methods, including the comparative molecular field analysis (CoMFA), the comparative molecular similarity indices analysis (CoMSIA), the molecular electrostatic potential (MEP) analysis and the docking method. Several 3D-QSAR models with proper reliability were well established, with a CoMFA model with steric and electrostatic fields exhibiting 0.67, 0.99 and 0.88 of q(2), r(2) and r(2) pred, respectively, a CoMSIA model with steric, electrostatic and H-bond acceptor fields displaying 0.72, 0.97 and 0.84 of q(2), r(2) and r(pred)(2), respectively. These models and related docking results reveal that quinidine binds to CYP2D6 in an inverse orientation as compared with quinine. Moreover, quinidine blocks the entrance of the active pocket of CYP2D6 more closely than quinine does, which explains well why the inhibitory activity of quinidine is of 2 magnitudes larger than quinine. This investigation provides a better understanding of the stereoisometric effects on the bioactivities of the chiral isomers quinidine and quinine interacting with CYP2D6. (C) 2008 Elsevier Ltd. All rights reserved.
关键词[WOS]: MOLECULAR-FIELD ANALYSIS ;  CYTOCHROME-P450 2D6 ;  BINDING ;  COMSIA ;  COMFA
语种: 英语
WOS记录号: WOS:000262707000051
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/141501
Appears in Collections:中国科学院大连化学物理研究所_期刊论文

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作者单位: 1.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian 116023, Peoples R China
2.Chinese Acad Sci, Grad Sch, Beijing 100049, Peoples R China
3.Dalian Univ Technol, Sch Chem Engn, Dalian 116012, Peoples R China
4.Dalian Fisheries Univ, Sch Life Sci & CBiotechnol, Dalian 116023, Peoples R China
5.China Pharmaceut Univ, Dept Basic Sci, Nanjing 210009, Peoples R China

Recommended Citation:
Ai, Chunzhi,Li, Yan,Wang, Yonghua,et al. Insight into the effects of chiral isomers quinidine and quinine on CYP2D6 inhibition[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2009,19(3):803-806.
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