Drug-drug interation prediction between ketoconazole and anti-liver cancer drug Gomisin G.

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.

• Authors: Liu Xiaoyang, Ni Chenming, Li Chengqing, Liu Tao
• Journal: African health sciences (Afr Health Sci) Vol. 15 Issue 2 Pg. 590-3 (Jun 2015) ISSN: 1729-0503 [Electronic] Uganda
• PMID: 26124807 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Cyclooctanes
• Cytochrome P-450 CYP3A Inhibitors
• Dioxoles
• Lignans
• Plant Extracts
• schizandrer A
• Cytochrome P-450 CYP3A
• Ketoconazole

Topics

• Antineoplastic Agents (administration & dosage, pharmacology)
• Cyclooctanes (chemistry, metabolism)
• Cytochrome P-450 CYP3A (chemistry)
• Cytochrome P-450 CYP3A Inhibitors (pharmacology)
• Dioxoles (chemistry, metabolism)
• Drug Interactions
• Humans
• Ketoconazole (pharmacology)
• Lignans (chemistry, metabolism)
• Liver (drug effects)
• Liver Neoplasms (drug therapy, metabolism)
• Molecular Docking Simulation
• Plant Extracts (chemistry)
• Schisandra (chemistry)