Liu Xiaoyang1, Ni Chenming2, Li Chengqing3, Liu Tao4. 1. Department of Hepatobiliary Surgery, Jinan Military General Hospital, Jinan 250031, P.R. China. 2. Laboratory of Pharmacology, Department of Pharmacy, Jinan Military General Hospital, Jinan 250031, P.R. China. 3. Department of General Surgery, No. 1 Hospital of People's Liberation Army, Lanzhou 730030, P.R. China. 4. Department of Dermatology, Tangdu Hospital, the Fourth Military Medical University, Xi'an 710038, P.R. China.
Abstract
BACKGROUND: Gomisin G, isolated from herb Schisandra chinensis, exhibits anti-tumor activities. Therefore, Gomisin G is a drug candidate for anti-liver cancer therapy. AIMS: To predict the metabolic behavior and metabolism-based drug-drug interaction of gomisin G. METHODS: Molecular docking method was used. The crystal structure of CYP3A4 with the ligand ketoconazole was chosen from protein data bank (http://www.rcsb.org/pdb). Chemdraw software was used to draw the two-dimensional structure of gomisin G with standard bond lengths and angles. RESULTS: Gomisin G can be well docked into the activity site of CYP3A4, and distance between gomisin G the heme active site was 2.75 Å. To evaluate whether the inhibitors of CYP3A4 can affect the metabolism of gomisin G, co-docking of gomisin G and ketoconazole was further performed. The distance between ketoconazole and activity center (2.10 Å) is closer than the distance between gomisin G and activity center of CYP3A4, indicating the easy influence of CYP3A4's strong inhibitor towards the metabolism of gomisin G. CONCLUSION: Gomisin G is a good substrate of CYP3A4, and CYP3A4 inhibitors easily affect the metabolism of Gomisin G.
BACKGROUND: Gomisin G, isolated from herb Schisandra chinensis, exhibits anti-tumor activities. Therefore, Gomisin G is a drug candidate for anti-liver cancer therapy. AIMS: To predict the metabolic behavior and metabolism-based drug-drug interaction of gomisin G. METHODS: Molecular docking method was used. The crystal structure of CYP3A4 with the ligand ketoconazole was chosen from protein data bank (http://www.rcsb.org/pdb). Chemdraw software was used to draw the two-dimensional structure of gomisin G with standard bond lengths and angles. RESULTS: Gomisin G can be well docked into the activity site of CYP3A4, and distance between gomisin G the heme active site was 2.75 Å. To evaluate whether the inhibitors of CYP3A4 can affect the metabolism of gomisin G, co-docking of gomisin G and ketoconazole was further performed. The distance between ketoconazole and activity center (2.10 Å) is closer than the distance between gomisin G and activity center of CYP3A4, indicating the easy influence of CYP3A4's strong inhibitor towards the metabolism of gomisin G. CONCLUSION: Gomisin G is a good substrate of CYP3A4, and CYP3A4 inhibitors easily affect the metabolism of Gomisin G.
Authors: John Gnabre; Irem Unlu; Tso-Cheng Chang; Paul Lisseck; Bryan Bourne; Ryan Scolnik; Neil E Jacobsen; Robert Bates; Ru Chih Huang Journal: J Chromatogr B Analyt Technol Biomed Life Sci Date: 2010-08-14 Impact factor: 3.205