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.

Gomisin G Inhibits the Growth of Triple-Negative Breast Cancer Cells by Suppressing AKT Phosphorylation and Decreasing Cyclin D1

“…Previous studies have demonstrated the anti-HIV, anti-liver cancer and anti-inflammatory capacity of Gomisin G, a wellknown natural compound extracted from Schisandra chinesis ( Chen et al ., 1997 ; Ryu et al ., 2011 ; Xiaoyang et al ., 2015 ). In this study, we explored the potential activity of Gomisin G as a novel and effective compound against TNBC.…”

“…Gomisins exhibit various therapeutic potential such as anti-inflammatory, anti-obesity, anti-oxidant, anti-cancer and liver protectant ( Choi et al ., 2006 ; Min et al ., 2008 ; Oh et al ., 2010 ; Park et al ., 2014 ; Jang et al ., 2017 ). One of the important components isolated from S. chinesis is Gomisin G, which has been reported to have anti-HIV, anti-liver cancer and anti-inflammatory activity ( Chen et al ., 1997 ; Ryu et al ., 2011 ; Xiaoyang et al ., 2015 ).…”

Effects of Ginkgo leaf tablets on the pharmacokinetics of losartan and its metabolite EXP3174 in rats and its mechanism

“…For example, the antifungal ketoconazole, a potent inhibitor of CYP3A4, causes drug–drug interactions with drugs that are substrates of CYP3A4 (Xiaoyang et al. 2015 ). Losartan was primarily metabolized by CYP3A4 and CYP2C19 in liver, and therefore, herbs or drugs that could affect the activity of CYP3A4 or CYP2C19 might influence the pharmacokinetics profiles of losartan when they are co-administered.…”

Gomisin G Suppresses the Growth of Colon Cancer Cells by Attenuation of AKT Phosphorylation and Arrest of Cell Cycle Progression

“…Gomisins, which are phytoestrogens, extracted from the fruits of Schisandra chinesis have traditionally been used in herbal medicine in Korea, China, Japan and Russia ( Opletal et al ., 2004 ; Choi et al ., 2006 ; Min et al ., 2008 ; Park et al ., 2014 ; Jang et al ., 2017 ). Gomisin G is a lignan from S. chinesis and was reported to have anti-HIV, anti-liver cancer and anti-inflammatory activities ( Chen et al ., 1997 ; Ryu et al ., 2011 ; Xiaoyang et al ., 2015 ). In a previous study, we found that Gomisin G has promise as a therapeutic agent against triple-negative breast cancer cells via an AKT-cyclin D1 dependent mechanism ( Maharjan et al ., 2018 ).…”