The study of drug resistance properties of ABCG2 (ATP-binding cassette G2) in contact with thymoquinone, gallic acid, and hesperetin antioxidants
| Autor: | Sayed Mohammad Shafiee, Keihan Ghatreh-Samani, Narges Jalilian, Javad Saffari Chaleshtori |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Medicine (General)
Stereochemistry Protein Data Bank (RCSB PDB) ATP-binding cassette transporter Cancer cell RM1-950 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine R5-920 ABCG2 transporter Drug Discovery Gallic acid Binding site Thymoquinone 030304 developmental biology chemistry.chemical_classification 0303 health sciences Hesperetin AutoDock Amino acid chemistry 030220 oncology & carcinogenesis embryonic structures sense organs Therapeutics. Pharmacology Antioxidant Simulation |
| Zdroj: | Journal of HerbMed Pharmacology, Vol 8, Iss 2, Pp 108-113 (2019) |
| ISSN: | 2345-5004 |
| Popis: | 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. ABCG2 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 ABCG2 compared with an anti-cancer drug, mitoxantrone (Mit), to export cells. Methods: The PDB file of ABCG2 was obtained from the protein data bank server (http://www.rcsb.org) with ID: 5NJ3. After 200 stages of molecular docking running on ABCG2 protein in AutoDock v.4.2 software, the amino acids involved in the binding site of each compound were identified using the LigPlot+ software. Results: HP had the lowest (-6.36 kcal/mol) and GA had the highest (-3.93 kcal/mol) binding energy in comparison with Mit (-0.06 kcal/mol) for binding to ABCG2. Effective concentration required to perform the reaction between ABCG2 was higher in GA (1.31 mM) than TQ (42.69 μM) and HP (21.74 μM). GA, HP, and TQ formed 17, 18, and 22 hydrogen and hydrophobic bonds at the binding site of ABCG2. Conclusion: It seems that GA has the lowest affinity to make contact with ABCG2 binding site. So, GA tends to remain in the cell but TQ and HP tend to leave the cell easily via ABCG2 transporter. |
| Databáze: | OpenAIRE |
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