科研之友
微信
新浪微博
Facebook
分享链接
摘要
More and more reports have showed the important role of inflammation in the pathogenesis of infectious disease, and the compounds with anti-inflammation activity are being developed as the infectious disease treatment drug. Bruceine B is a promissory anti-infectious disease drug due to its anti-inflammation activity. The present study aims to predict the drug-drug interaction between bruceine B and ketoconazole which has also been applied in the anti-infectious disease therapy. The first step of this study is to select the protein structure of CYP3A4. In the database, several crystal structures can be found, such as the crystal structure of CYP3A4 in complex with ketoconazole (code: 2V0M), the crystal structure of CYP3A4 in complex with erythromycin (2J0D), and the crystal structure of CYP3A4 in complex with ritonavir (3NXU). In the present study, to study the drug-drug interaction, the protein structure with the code 2VOM was select, and the ligand ketoconazole was extracted from the activity cavity. Bruceine B can well dock into the activity center through the strong hydrogen bond interaction with Ser119 in thee protein structure. The distance between metabolic site and the catalytic center was calculated to be 3.65 angstrom. When co-docking ketoconazole and bruceine B into the activity cavity, the distance between ketoconazole and the catalytic center is closer than the distance between brutceine B and the catalytic center of CYP3A4. hi conclusion, CYP3A4-mediated drug-drug interaction between ketoconazole and bruceine B was predicted, indicating that more caution should be paid on the clinical co-administration of bruceine B and ketoconazole.
- 出版日期2015-11
- 单位中南大学
