2015年10月
Identification and in silico prediction of metabolites of the model compound, tebufenozide by human CYP3A4 and CYP2C19
BIOORGANIC & MEDICINAL CHEMISTRY
- 巻
- 23
- 号
- 20
- 開始ページ
- 6594
- 終了ページ
- 6601
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.bmc.2015.09.019
- 出版者・発行元
- PERGAMON-ELSEVIER SCIENCE LTD
The metabolites of tebufenozide, a model compound, formed by the yeast-expressed human CYP3A4 and CYP2C19 were identified to clarify the substrate recognition mechanism of the human cytochrome P450 (CYP) isozymes. We then determined whether tebufenozide metabolites may be predicted in silico. Hydrogen abstraction energies were calculated with the density functional theory method B3LYP/6-31G*. A docking simulation was performed using FRED software. Several alkyl sites of tebufenozide were hydroxylated by CYP3A4 whereas only one site was modified by CYP2C19. The accessibility of each site of tebufenozide to the reaction center of CYP enzymes and the susceptibility of each hydrogen atom for metabolism by CYP enzymes were evaluated by a docking simulation and hydrogen abstraction energy estimation, respectively. (c) 2015 Elsevier Ltd. All rights reserved.
- リンク情報
- ID情報
-
- DOI : 10.1016/j.bmc.2015.09.019
- ISSN : 0968-0896
- eISSN : 1464-3391
- PubMed ID : 26404412
- Web of Science ID : WOS:000362379200007