DICP OpenIR
学科主题物理化学
Recent density functional theory model calculations of drug metabolism by cytochrome P450
Li, Dongmei1,2; Wang, Yong1; Han, Keli1; Han KL(韩克利)
关键词Density Functional Theory Compound i Hydrogen Atom Transfer Two-state Reactivity
刊名COORDINATION CHEMISTRY REVIEWS
2012-06-01
DOI10.1016/j.ccr.2012.01.016
256期:11-12页:1137-1150
收录类别SCI
文章类型Review
部门归属11
项目归属1101
产权排名1,1
类目[WOS]Chemistry, Inorganic & Nuclear
研究领域[WOS]Chemistry
关键词[WOS]C-H HYDROXYLATION ; ISOTOPE EFFECT PROFILES ; HUMAN LIVER-MICROSOMES ; FUNDAMENTAL REACTION PATHWAYS ; CATALYZED N-DEMETHYLATION ; COMPOUND-I ; SUBSTITUTED N,N-DIMETHYLANILINES ; REBOUND MECHANISM ; HYDROGEN ABSTRACTION ; ELECTRONIC-STRUCTURE
英文摘要Cytochrome P450 (P450) enzymes are the major catalysts involved in the oxidative metabolism of most drugs, steroids, carcinogens, and other chemicals. They catalyze a variety of reactions and convert chemicals to potentially reactive products as well as make compounds less toxic. More than 75% of drugs in clinical use are metabolized by P450s. Understanding the mechanism of drug metabolism by P450, in particular the chemical process, is indispensable in the early phases of drug discovery process. In this review, we discuss our recent theoretical studies on the mechanism of some specific compounds catalyzed by P450. Density functional theory (DFT) is used as the quantum mechanical (QM) tool to explore the fundamental mechanism of these reactions. These DFT calculations provide structures, energies, and some other properties of transition states and intermediates and thus shed light on the electronic factors that govern the stability and reactivity. These theoretical studies provide a complementary insight to experiment and suggest some new features. DFT serves a powerful tool to explore the chemical mechanism of drug metabolism by P450. The revealed fundamental mechanism concerning how the enzyme catalyzes the drug metabolism, especially the transition state of the rate-determining reaction step, could provide a valuable mechanistic base for rational design of novel drugs. (C) 2012 Elsevier B.V. All rights reserved.
语种英语
WOS记录号WOS:000303787500005
引用统计
被引频次:73[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://cas-ir.dicp.ac.cn/handle/321008/117813
专题中国科学院大连化学物理研究所
通讯作者Han KL(韩克利)
作者单位1.Chinese Acad Sci, Dalian Inst Chem Phys, State Key Lab Mol React Dynam, Dalian 116023, Peoples R China
2.Nankai Univ, Coll Pharm, Tianjin 300071, Peoples R China
推荐引用方式
GB/T 7714
Li, Dongmei,Wang, Yong,Han, Keli,et al. Recent density functional theory model calculations of drug metabolism by cytochrome P450[J]. COORDINATION CHEMISTRY REVIEWS,2012,256(11-12):1137-1150.
APA Li, Dongmei,Wang, Yong,Han, Keli,&韩克利.(2012).Recent density functional theory model calculations of drug metabolism by cytochrome P450.COORDINATION CHEMISTRY REVIEWS,256(11-12),1137-1150.
MLA Li, Dongmei,et al."Recent density functional theory model calculations of drug metabolism by cytochrome P450".COORDINATION CHEMISTRY REVIEWS 256.11-12(2012):1137-1150.
条目包含的文件
文件名称/大小 文献类型 版本类型 开放类型 使用许可
2012uw04umZTDP.PDF(1469KB) 开放获取--请求全文
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Li, Dongmei]的文章
[Wang, Yong]的文章
[Han, Keli]的文章
百度学术
百度学术中相似的文章
[Li, Dongmei]的文章
[Wang, Yong]的文章
[Han, Keli]的文章
必应学术
必应学术中相似的文章
[Li, Dongmei]的文章
[Wang, Yong]的文章
[Han, Keli]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。