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UNIVERSITY OF BUCHAREST
FACULTY OF PHYSICS Guest
2024-11-22 2:15 |
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Conference: Bucharest University Faculty of Physics 2024 Meeting
Section: Biophysics; Medical Physics
Title:
Evaluation of silymarin and curcumin as potential pan-FGFR inhibitors through a molecular docking approach
Authors:
Adina Monica TODERAČ, Darius Maximilian MANGRA
Affiliation:
University of Oradea
E-mail
atoderas@uoradea.ro, maximilianmangra@gmail.com
Keywords:
molecular docking, curcumin, silymarin, FGFR, inhibition
Abstract:
FGFRs represent a protein family comprising four transmembrane receptor tyrosine kinases (RTK). They are fundamental to the PI3K/ AKT/mTOR signaling pathway, which regulates survival, cell proliferation and differentiation. Two polyphenols, Silymarin and Curcumin, have demonstrated encouraging outcomes in in vitro investigations. Consequently, this research aims to assess their theoretical pan-FGFR inhibitory potential through molecular docking simulations. We compared the outcomes of futibatinib (a covalent, non-selective FGFR inhibitor), lirafugratinib (a covalent-selective FGFR2 inhibitor), resigratinib (a pan-FGFR inhibitor), and Blu9931 (a covalent FGFR4 inhibitor) with those of silymarin and curcumin. The polyphenols did not demonstrate lower binding energies compared to the co-crystallized ligands, and their inhibition constants were also higher. Nevertheless, our observations revealed that curcumin and silymarin successfully formed hydrogen bonds with the specific Cysteine residue in some cases. Silymarin formed a hydrogen bond in FGFR 1, 3, and 4, while curcumin did so in FGFR3 and 4. This suggests their potential as adjuvant methods in pan-FGFR inhibition. Aditionally, the polyphenols examined obey to Lipinski's rule, and their various ADMET properties have also been assessed.
References:
1. Rahimi N., 2017. Defenders and Challengers of Endothelial Barrier Function. Frontiers in Immunology, 8(1847), 1-10, 2017
2. Rawluk J., Waller C.F., Gefitinib. Recent Results Cancer Research, 211, 235-246, 2018
3. Golonko A. et al., Curcumin as Tyrosine Kinase Inhibitor in Cancer Treatment. European Journal of Medicinal Chemistry, 181, 111512, 1-25, 2019
4. Hamzehzadeh, L. et al., 2018. The Versatile Role of Curcumin in Cancer Prevention and Treatment: A Focus on PI3K/AKT Pathway. Journal of Cellular Physiology, 233(10), pp.6530-6537.
5. Papadimitrakopoulou V., Development of PI3K/AKT/mTOR Pathway Inhibitors and Their Application in Personalized Therapy for Non -Small-Cell Lung Cancer. Journal of Thorac Oncology, 7(8), 1315-1326, 2012
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