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Insight into the effects of chiral isomers quinidine and quinine on CYP2D6 inhibition
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
2009-02-01
DOI10.1016/j.bmcl.2008.12.016
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
关键词[WOS]MOLECULAR-FIELD ANALYSIS ; CYTOCHROME-P450 2D6 ; BINDING ; COMSIA ; COMFA
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.
语种英语
WOS记录号WOS:000262707000051
引用统计
文献类型期刊论文
条目标识符http://cas-ir.dicp.ac.cn/handle/321008/141501
专题中国科学院大连化学物理研究所
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
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GB/T 7714
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.
APA Ai, Chunzhi,Li, Yan,Wang, Yonghua,Chen, Yadong,&Yang, Ling.(2009).Insight into the effects of chiral isomers quinidine and quinine on CYP2D6 inhibition.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,19(3),803-806.
MLA Ai, Chunzhi,et al."Insight into the effects of chiral isomers quinidine and quinine on CYP2D6 inhibition".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 19.3(2009):803-806.
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