Javad Saffari_Chaleshtori
Sayed Mohammad Shafiee
Keihan Ghatreh-Samani
Narges Jalilian

Introduction: ATP-binding cassette (ABC) transporters are a group of intra membrane proteins that play key roles in the transmission and exchange of vital compounds on both sides of the membrane. These proteins can specially transport anti-cancer drugs out of cancer cells. ABCG۲ is a member of this family that is extremely expressed in many cancers. This study, aims to evaluate the binding affinity of three antioxidants thymoquinone (TQ), gallic acid (GA), and hesperetin (HP) to ABCG۲ compared with an anti-cancer drug, mitoxantrone (Mit), to export cells. Methods: The PDB file of ABCG۲ was obtained from the protein data bank server (http://www.rcsb.org) with ID: ۵NJ۳. After ۲۰۰ stages of molecular docking running on ABCG۲ protein in AutoDock v.۴.۲ software, the amino acids involved in the binding site of each compound were identified using the LigPlot+ software. Results: HP had the lowest (-۶.۳۶ kcal/mol) and GA had the highest (-۳.۹۳ kcal/mol) binding energy in comparison with Mit (-۰.۰۶ kcal/mol) for binding to ABCG۲. Effective concentration required to perform the reaction between ABCG۲ was higher in GA (۱.۳۱ mM) than TQ (۴۲.۶۹ μM) and HP (۲۱.۷۴ μM). GA, HP, and TQ formed ۱۷, ۱۸, and ۲۲ hydrogen and hydrophobic bonds at the binding site of ABCG۲. Conclusion: It seems that GA has the lowest affinity to make contact with ABCG۲ binding site. So, GA tends to remain in the cell but TQ and HP tend to leave the cell easily via ABCG۲ transporter.