Potential Repurposing N-heterocyclic Drugs for Epidermal Growth Factor Receptor Inhibition: A Theoretical Study
Main Article Content
Abstract
This study investigates the repurposing of 40 approved drugs containing N-heterocyclic as epidermal growth factor receptor (EGFR) inhibitors using molecular docking with AutoDock 4. Through crystal structure analysis, input preparation, search space definition, and docking execution, ligands are categorized into weak, medium, and strong binders. Notably, ibrutinib, bedaquiline, rimonabant and lapatinib exhibit strong interactions, while fezolamine shows weaker binding. The study suggests the potential of N-heterocyclic compounds for EGFR inhibition and offers insights relevant to new drug development.
Keywords:
N-heterocyclic containing drugs, AutoDock, epidermal growth factor receptor, epidermal growth factor receptor inhibitor.
References
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[4] Z. Zhang, L. Zhou, N. Xie, E. Nice, T. Zhang, Y. Cui, and C. Huang, Overcoming cancer therapeutic bottleneck by drug repurposing, Signal Transduction and Targeted Therapy, Vol. 5, 2020, https://doi.org/10.1038/s41392-020-00213-8.
[5] M. Heravi and V. Zadsirjan, Prescribed drugs containing nitrogen heterocycles: an overview, RSC Advances, Vol. 10, 2020, pp. 44247-44311, https://doi.org/10.1039/d0ra09198g.
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[7] V. Rusch, J. Mendelsohn, and E. Dmitrovsky, The epidermal growth factor receptor and its ligands as therapeutic targets in human tumors, Cytokine & Growth Factor Reviews, Vol. 7, No. 2, 1996, pp. 133-141, https://doi.org/10.1016/1359-6101(96)00016-0.
[8] C. Yewale, D. Baradia, I. Vhora, S. Patil, and A. Misra, Epidermal growth factor receptor targeting in cancer: a review of trends and strategies, Biomaterials, Vol. 34, No. 34, 2013, pp. 8690-8707, https://doi.org/10.1016/j.biomaterials.2013.07.100.
[9] J. Pham, A. Rodrigues, S. Goldinger, H. W. Sim, and J. Liu, Epidermal growth factor receptor inhibitors in advanced cutaneous squamous cell carcinoma: A systematic review and meta-analysis, Experimental Dermatology, Vol. 33, 2023, https://doi.org/10.1111/exd.14978.
[10] C. Ho, A. Davies, P. Mack, and D. Gandara, Dual inhibition: combining epidermal growth factor-targeted therapies in non-small-cell lung cancer, Clinical Lung Cancer, Vol. 8, No. 7, 2007, pp. 420-424, https://doi.org/10.3816/CLC.2007.N.025.
[11] D. W. Fry, Inhibition of the epidermal growth factor receptor family of tyrosine kinases as an approach to cancer chemotherapy: progression from reversible to irreversible inhibitors, Pharmacology & Therapeutics, Vol. 82, No. 2-3, 1999, pp. 207-218.
[12] A. Ayati, S. Moghimi, S. Salarinejad, M. Safavi, B. Pouramiri, and A. Foroumadi, A review on progression of epidermal growth factor receptor (EGFR) inhibitors as an efficient approach in cancer targeted therapy, Bioorganic Chemistry, Vol. 99, 2020, pp. 103811, https://doi.org/10.1016/j.bioorg.2020.103811.
[13] F. Gentile, V. Agrawal, M. Hsing, A. Ton, F. Ban, U. Norinder, M. Gleave, and A. Cherkasov, Deep Docking: A Deep Learning Platform for Augmentation of Structure Based Drug Discovery, ACS Central Science, Vol. 6, 2020, pp. 939-949, https://doi.org/10.1021/acscentsci.0c00229.
[14] M. De Vivo and A. Cavalli, Recent advances in dynamic docking for drug discovery, Wiley Interdisciplinary Reviews: Computational Molecular Science, Vol. 7, 2017, https://doi.org/10.1002/wcms.1320.
[15] D. Gioia, M. Bertazzo, M. Recanatini, M. Masetti, and A. Cavalli, Dynamic Docking: A Paradigm Shift in Computational Drug Discovery, Molecules, Vol. 22, 2017, https://doi.org/10.3390/molecules22112029.
[16] R. B. Silverman and M. W. Holladay, The Organic Chemistry of Drug Design and Drug Action, Amsterdam: Elsevier, 2014.
[17] A. Tomasz, The Mechanism of the Action of Beta-Lactam Antibiotics, Annual Review of Medicine, Vol. 30, 1979, pp. 121-131, https://doi.org/10.1146/annurev.me.30.020179.001005.
[18] M. O. Glocker, et al., Sulfonamides and Their Use in Anti-inflammatory Therapies, Current Medicinal Chemistry, Vol. 20, No. 6, 2013, pp. 786-803.
[19] A. Ullah, et al., Folate Metabolism Pathways in Health and Disease, Asian Pacific Journal of Cancer Prevention, Vol. 17, No. 2, 2016, pp. 513-515.
[20] R. Stefan, ACE Inhibitors in the Treatment of Cardiovascular Disorders, European Heart Journal, Vol. 25, No. 3, 2004, pp. 202-205, https://doi.org/10.1016/j.ehj.2003.11.003.
[21] J. S. Davies, et al., The Role of Bicyclic Frameworks in Pharmacology, Journal of Medicinal Chemistry, Vol. 48, No. 8, 2005, pp. 2651-2661.
[22] R. A. Dixon, The Fluoroquinolones: Update on Their Use and Mechanism of Action, Clinical Pharmacology & Therapeutics, Vol. 87, No. 1, 2010, pp. 13-17.
[23] J. G. Hardman, L. E. Limbird, and A. G. Gilman, Goodman & Gilman's The Pharmacological Basis of Therapeutics, New York: McGraw-Hill, 2001.
[24] E. H. Kerns and L. Di, Drug-like Properties: Concepts, Structure Design, and Methods, Amsterdam: Elsevier, 2008.
[25] P. Klatt, et al., Structural Insights into Selective Binding of Statins, Biochemistry, Vol. 43, No. 6, 2004, pp. 1630-1640.
[26] C. G. Wermuth, The Practice of Medicinal Chemistry, San Diego: Academic Press, 2003.