[Home ] [Archive]   [ فارسی ]  
:: Main :: About :: Current Issue :: Archive :: Search :: Submit :: Contact ::
Main Menu
Journal Information::
Articles archive::
Publication Ethics::
Peer Review Process::
Indexing Databases::
For Authors::
For Reviewers::
Contact us::
Site Facilities::
Google Scholar Metrics

Citation Indices from GS

AllSince 2018

Search in website

Advanced Search
Receive site information
Enter your Email in the following box to receive the site news and information.
Registered in



:: Volume 30, Issue 2 (6-2022) ::
Journal of Ilam University of Medical Sciences 2022, 30(2): 32-40 Back to browse issues page
Study of Human Albumin Protein Interaction with Fluorouracil Anticancer Drug Using Molecular Docking Method
Mohammad Motaharinia1 , Mahdieh Sadeghpour * 2, Monir Shalbafan3
1- Dept of Chemistry, Takestan Branch, Islamic Azad University, Takestan, Iran
2- Dept of Chemistry, Takestan Branch, Islamic Azad University, Takestan, Iran , m.sadeghpour@tiau.ac.ir
3- Dept of chemistry, Imam Khomeini International University, Qazvin, Iran
Abstract:   (2401 Views)
Introduction: Drugs are mainly delivered to the target tissues by plasma proteins, such as human serum albumin, in the human body. Practical information about the thermodynamic parameters of drugs and their stability can be obtained using simulation methods, such as molecular docking.
Material & Methods: This study, investigated the molecular docking of human serum albumin with fluorouracil anticancer drug. Moreover, partial charges on serum albumin protein atoms and fluorouracil atoms were calculated in this study. The best configuration was also searched using the Lamarckian genetic algorithm. The dimensions of the grid maps were selected to be about 40 * 40 * 40 angstroms with a distance of 0.375 angstroms. The number of genetic algorithms and the number of studies were adjusted to about 100 and 2.5 million, respectively. In the end, the best performed interaction configurations with the least amount of free energy were selected. Ligplot and VMD graphic software were used to view the performed docking.
Findings: In the best model, fluorouracil is able to bind to the human serum albumin protein HSA four hydrogen bonds via nitrogen and oxygen atoms with two amino acids tyrosine, one amino acid histidine and one amino acid arginine. The estimation of the free bond energies (kcal/mol) for the best model was -5.1. Negative Gibbs free energy values (ΔG °) indicated a spontaneous process, and a constant binding value (Ka ≈ 109 L • mol-1) demonstrated the optimal biological distribution of the drug in the blood plasma.
Discussion & Conclusion: The docking study of the proposed models shows that fluorouracil has an aliphatic ring and hydrophobic fractions and therefore it has a high ability to form hydrophobic interactions with major amino acids at the active site of serum albumin protein.

Keywords: Anti-cancer drug, Binding constant, Fluorouracil, Gibbs free energy, Human serum albumin
Full-Text [PDF 1411 kb]   (533 Downloads)    
Type of Study: Research | Subject: General
Received: 2021/01/30 | Accepted: 2021/11/29 | Published: 2022/06/5
1. Fitzmaurice C, Allen C, Barber R, Barregard L, Bhutta Z, Brenner H, et al. Global, regional and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: A systematic analysis for the global burden of disease study global burden of disease cancer collaboration. JAMA Oncol 2017;3: 524-48. doi: 10.1001/jamaoncol.2016.5688
2. Fernandez EJ. Allosteric pathways in nuclear receptors potential targets for drug design. Pharmacol Ther 2018; 183: 152-9. doi: 10.1016/j.pharmthera.2017.10.014
3. Willis RE. Targeted cancer therapy vital oncogenes and a new molecular genetic paradigm for cancer initiation progression and treatment. Int J Mol Sci 2016; 17: 1552-75. doi: 10.3390/ijms17091552
4. Nooridaloii M, Tabarestani S. Molecular genetics and gene therapy in breast cancer a review article. J Sabzevar Uni Med Sci 2010; 17:74-87. doi: 10.29252/iau.28.4.259
5. Nooridaloii M, Zekri A. Aura kinase family roles in cancer diagnosis and treatment a review article. Med Sci J Islamic Azad Uni Tehran 2011; 21: 71-81.
6. Sawyers C. Targeted cancer therapy. Nature 2004; 432: 294-7. doi: 10.1038/nature03095
7. Vulfovich M, Saba N. Molecular biological design of novel antineoplastic therapies. Expert Opin Investig Drugs 2004; 13: 577-607. doi: 10.1517/13543784.13.6.577
8. Olgen S. Overview on anticancer drug design and development. Curr Med Chem 2018; 25: 1704-19. doi: 10.2174/0929867325666171129215610
9. Neidle S. Cancer drug design and discovery. Book Published 2014; doi: 10.1016/C2011-0-07765-7
10. Magalhaes LG, Ferreira LLG, Andricopulo AD. Recent advances and perspectives in cancer drug design. An Acad Bras Cienc 2018; 14: 1233-50. doi: 10.1590/0001-3765201820170823
11. Cui W, Aouidate A, Wang S, Yu Q, Li Y, Yuan S. Discovering anti-cancer drugs via computational methods. Front Pharmacol 2020; 11: 1-14. doi: 10.3389/fphar.2020.00733
12. Torres PHM, Sodero ACR, Jofily P, Silva JRFP. Key topics in molecular docking for drug design. Int J Mol Sci 2019; 20: 4574-603. doi: 10.3390/ijms20184574
13. Wang G, Zhu W. Molecular docking for drug discovery and development a widely used approach but far from perfect. Future Med Chem 2016; 8: 1707-10. doi: 10.4155/fmc-2016-0143
14. Sethi A, Khusbhoo J, Sasikala K, Alvala M. Molecular docking in modern drug discovery principles and recent applications. Book Published 2019; doi: 10.5772/intechopen.85991
15. Ruyck J, Brysbaert G, Blossey R, Lensink M. Molecular docking as a popular tool in drug design, an in silico travel. Adv Appl Bioinform Chem 2016; 9: 1-11. doi: 10.2147/AABC.S105289
16. Jakhar R, Dangi M, Khichi A, Chhillar AK. Relevance of molecular docking studies in drug designing. Curr Bioinformatics 2020; 15: 270-78. doi:10.2174/1574893615666191219094216
17. Collins I, Workman P. New approaches to molecular cancer therapeutics. Nat Chem Biol 2006; 2: 689-700. doi: 10.1038/nchembio840
18. Wadood A, Ahmed N, Shah L, Ahmad A, Hassan H, Shams S. In-silico drug design: An approach which revolutionarised the drug discovery process. OA drug design & delivery 2013; 1:3-7. doi: 10.13172/2054- 4057-1-1-1119
19. Meng XY, Zhang HX, Mezei M, Cui M. Molecular docking a powerful approach for structure based drug discovery. Curr Comput Aided Drug Des 2011; 7: 146-57. doi: 10.2174/157340911 795677602
20. Bhogale A, Patel N, Mariam J, Dongre PM, Miotello A, Kothari DC. Comprehensive studies on the interaction of copper nanoparticles with bovine serum albumin using various spectroscopies. Colloids Surf B Biointerfaces 2014; 113: 276-84. doi: 10.1016/j.colsurfb.2013.09.021
21. Chen L, Wu M, LinX, Xie Z. Study on the interaction between human serum albumin and a novel bioactive acridine derivative using optical spectroscopy. Luminescence 2011; 26: 172-7. doi: 10.1002/bio.1201
22. Yang H, Huang Y, Liu J, Tang P, Sun Q, Xiong X, et al. Binding modes of environmental endocrine disruptors to human serum albumin insights from STD-NMR, ITC, spectroscopic and molecular docking studies. Sci Rep 2017; 7:11126-37. doi: 10.1038/s41598-017-11604-3
23. Markovic OS, Cvijetic IN, Zlatovic MV, Opsenica IM, Konstantinovic JM, Terzic Jovanovic NV, et al. Human serum albumin binding of certain antimalarial. Spectrochim. Acta A Mol Biomol Spectrosc 2018; 192: 128-36. doi: 10.1016/j.saa. 2017.10.061
24. Mihaelamic AP, Neamţu S, Floare CG, Bogdan M. Calorimetric and spectroscopic studies of the interaction between zidovudine and human serum albumin. Spectrochimica Acta Part A: Spectrochim. Acta A Mol Biomol Spectrosc 2018; 191: 226-32. doi: 10.1016/j.saa.2017.10.032
25. Yamasakia K, Nishic K, Anrakua M, Taguchia K, Maruyamad T, Otagiri M, Metal catalyzed oxidation of human serum albumin does not alter the interactive binding to the two principal drug binding sites. Biochem Biophys Rep. 2018; 14: 155-60. doi: 10.1016/j.bbrep.2018.05.002
26. Shiyovich A, Sasson L, Lev E, Solodky A, Kornowski R, Perl L. Relation of hypoal-buminemia to response to aspirin in patients with stable coronary artery disease. Am J Cardiol 2020; 125: 303-8. doi: 10.1016/j.amjcard. 2019.10.055
27. Rahnama E, Mahmoodianmoghaddam M, Khorsandahmadi, S, Saberi MR, Chamani J. Binding site identification of metformin to human serum albumin and glycated human serum albumin by spectroscopic and molecular modeling techniques a comparison study. J Biomol Struct Dyn2015; 33: 513-33. doi:10.1080/07391102. 2014.893540
28. Litus EA, Kazakov AS, Deryusheva EI, Nemashkalova EL, Shevelyova MP, Nazipova AA, et al. Serotonin promotes serum albumin interaction with the monomeric amyloid β peptide. Int J Mol Sci 2021; 22: 5896-910. doi: 10.3390/ ijms22115896
29. Fleming RA, Milano G, Thyss A, Etienne MCh, Renee N, Schneider M, et al. Correlation between dihydropyrimidine dehydrogenase activity in peripheral mononuclear cells and systemic clearance of fluorouracil in cancer atients. Cancer Res1992; 52:2899-902
30. Ghafourifard S, Abak A, Tondro anamag F, Shoorei H, Fattahi F, et al. 5-Fluorouracil: A Narrative review on the role of regulatory mechanisms in driving resistance to this chemotherapeutic agent. Front Oncol 2021; 11: 1-21. doi: 10.3389/fonc.2021.658636
31. Christensen SH, Roest B, Besselink N, Janssen R, Boymans S, Artens JWM, et al. 5-Fluorouracil treatment induces characteristic T>G mutations in human cancer. Nat Commun 2019; 10: 4571-82.doi:10.1038/s41467-019-12594-8
32. Parsa NZ, Mukherjee AB, Gaidano G, Hauptschein RS, Dallafavera R, Lenoir G. Cytogenetic and molecular analyis of 6q deletions in Burkitt΄s lymphoma cell lines. Genes Chromosom Cancer 1994; 9: 13-8. doi: 10.1002/gcc.2870090104.
33. Paal K, Shkarupin A, Beckford L. Paclitaxel binding to human serum albumin automated docking studies. Bioorg Med Chem 2007; 15: 1323-9. doi: 10.1016/j.bmc.2006.11.012
34. Ajmal MR, Nusrat S, Alam P, Zaidi N, Khan MV, Zaman M. Interaction of anticancer drug clofarabine with human serum albumin and human α-1 acid glycoprotein. Spectroscopic andmolecular docking approach. J Pharm Biomed Anal 2017; 135: 105-6. doi: 10.1016/j.jpba.2016.12.001.
35. Sun Z, XuH, Cao Y, Wang F, Mi W. Elucidating the interaction of propofol and serum albumin byspectroscopic and docking methods. J Mol Liq 2016; 219: 405-10. doi: 10.1016/j.molliq. 2016.03.040.
36. Heydargoy MH. Investigation of antiviral drugs with direct effect on RNA polymerases and simulation of their binding to SARS-CoV-2 RNA dependent RNA polymerase by molecular docking method. Iran J Microbiol 2020; 14: 342-7. doi: 10.30699/ijmm.14.4.342.
37. Yuriev E, Holien J, Ramsland PA. Improvements, trends and new ideas in molecular docking 2012-2013 in review. J Mol Recognit 2015; 28: 581-604. doi: 10.1002/jmr.2471
Send email to the article author

Add your comments about this article
Your username or Email:


Ethics code: 1

XML   Persian Abstract   Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Motaharinia M, Sadeghpour M, Shalbafan M. Study of Human Albumin Protein Interaction with Fluorouracil Anticancer Drug Using Molecular Docking Method. J. Ilam Uni. Med. Sci. 2022; 30 (2) :32-40
URL: http://sjimu.medilam.ac.ir/article-1-6983-en.html

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Volume 30, Issue 2 (6-2022) Back to browse issues page
مجله دانشگاه علوم پزشکی ایلام Journal of Ilam University of Medical Sciences
Persian site map - English site map - Created in 0.16 seconds with 41 queries by YEKTAWEB 4625