Recent density functional theory model calculations of drug metabolism by cytochrome P450
文献类型：期刊论文
| 作者 | Li, Dongmei1,2; Wang, Yong1; Han, Keli1 |
| 刊名 | coordination chemistry reviews
 |
| 出版日期 | 2012-06-01 |
| 卷号 | 256期号:11-12页码:1137-1150 |
| 关键词 | Density functional theory Compound I Hydrogen atom transfer Two-state reactivity |
| 产权排序 | 1,1 |
| 通讯作者 | 韩克利 |
| 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. |
| 学科主题 | 物理化学 |
| 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 |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000303787500005 |
| 公开日期 | 2013-10-11 |
| 源URL | [http://159.226.238.44/handle/321008/117813]  |
| 专题 | 大连化学物理研究所_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, 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. 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.(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. |
入库方式： OAI收割
来源：大连化学物理研究所
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