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In Silico Studies of a Novel Scaffold of Acetylsalicylic Acid Derivatives Against EGFR by Molecular Docking and Molecular Dynamics Simulations

Year 2024, , 274 - 281, 30.06.2024

Alpaslan Bayrakdar

https://doi.org/10.17776/csj.1410033

Abstract

In this study, a molecular docking study was performed to propose the acetylsalicylic acid derivative 2-[(4-Acetylphenyl)carbamoyl]phenyl acetate (AMPBS) as a potential cancer candidate targeting the Epidermal Growth Factor Receptor (EGFR). The native ligand erlotinib was used as a control compound. The calculated docking score of -7.4 kcal/mol compared to the native ligand erlotinib of -7.0 kcal/mol of AMPBS compound revealed a promising anticancer activity. The stability of the complex was interpreted by careful analysis of the root mean square deviation (RMSD), root mean square fluctuations (RMSF) and mean hydrogen bond number (Hb) plots obtained from the MD trajectories. The ADMET properties of AMPBS were evaluated using relevant online tools. Drug-likeness studies showed that AMPBS is suitable for use in living organisms. It was predicted that AMPBS in the active pocket could be a promising inhibitor due to its high binding energy, interaction mechanism and retention in the active pocket.

Keywords

DFT Molecular docking Molecular dynamic Acetylsalicylic acid ADMET

Thanks

I would like to acknowledge the support provided by the project Grant No: 2013FBE013 at Pamukkale University.

References

  • [1] Jemal A., Bray F., Center M.M., Ferlay J., Ward E., Forman D., Global cancer statistics, CA Cancer J. Clin., 61 (2) (2011) 69-90.
  • [2] Shang D., Sun D., Shi C., Xu J., Shen M., Hu X., Liu H., Tu Z., Activation of epidermal growth factor receptor signaling mediates cellular senescence induced by certain pro‐inflammatory cytokines, Aging Cell, 19 (5) (2020) e13145.
  • [3] Ukirde R., Sawant R., Nerkar A., Role of Epidermal Growth Factor Receptor Inhibitors in Treating Cancer, Curr Trends Pharm Pharm Chem, 2 (1) (2020) 57-63.
  • [4] Stamos J., Sliwkowski M.X., Eigenbrot C., Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor, J. Biol. Chem., 277 (48) (2002) 46265-46272.
  • [5] Cordover E., Minden A., Lehman S., Zhao O., Signaling pathways downstream to receptor tyrosine kinases: Targets for cancer treatment, J. Cancer Metastatis Treat., 2020 (2020) 1-19.
  • [6] Raymond E., Faivre S., Armand J.P., Epidermal growth factor receptor tyrosine kinase as a target for anticancer therapy, Drugs, 60 (2000) 15-23.
  • [7] Ahmad, A. A., Hussain, K., Shah, M. R., Ashhad Halimi, S. M., Rabbi, F., Ahmad, Z., Khan, I., Rauf, A., Alshammari, A., Rasul Suleria, H. A. (2023). Molecular Insights into the In Vivo Analgesic and Anti-Inflammatory Activity of Indomethacin Analogues, ACS Omega, 8(33), 30048-30056.
  • [8] Das A.J., Das M.K., Singh S.P., Saikia P.P., Singh N., Islam J., Ansari A., Chattopadhyay P., Rajamani P., Miyaji T., Synthesis of salicylic acid phenylethyl ester (SAPE) and its implication in immunomodulatory and anticancer roles, Sci. Rep., 12(1) (2022) 8735.
  • [9] Thiruchenthooran V., Sánchez-López E., Gliszczyńska A., Perspectives of the application of non-steroidal anti-inflammatory drugs in cancer therapy: Attempts to overcome their unfavorable side effects, Cancers, 15 (2) (2023) 475.
  • [10] Ramos-Inza S., Ruberte A.C., Sanmartin C., Sharma A.K., Plano D., NSAIDs: Old Acquaintance in the Pipeline for Cancer Treatment and Prevention─ Structural Modulation, Mechanisms of Action, and Bright Future, J. Med. Chem., 64(22) (2021) 16380-16421.
  • [11] Mohamed-Ezzat R.A., Kariuki B.M., Srour A.M., Synthesis, crystal structure and in vitro anti-proliferative activity of 2-[(4-acetylphenyl) carbamoyl] phenyl acetate, Acta Cryst. E, 79 (11) (2023).
  • [12] Ibrahim M.T., Uzairu A., Shallangwa G.A., Uba S., Structure-based design and activity modeling of novel epidermal growth factor receptor kinase inhibitors; an in silico approach, Sci. Afr., 9 (2020) e00503.
  • [13] Lin S.-Y., Chang Hsu Y., Peng Y.-H., Ke Y.-Y., Lin W.-H., Sun H.-Y., Shiao H.-Y., Kuo F.-M., Chen P.-Y., Lien T.-W., Discovery of a furanopyrimidine-based epidermal growth factor receptor inhibitor (DBPR112) as a clinical candidate for the treatment of non-small cell lung cancer, J. Med. Chem., 62 (22) (2019) 10108-10123.
  • [14] GaussView V., 6.1, R. Dennington, T.A. Keith, J.M. Millam, Semichem Inc, (2016).
  • [15] Frisch M., Trucks G., Schlegel H., Scuseria G., Robb M., Cheeseman J., Scalmani G., Barone V., Petersson G., Nakatsuji H., Gaussian 16 Rev. C. 01, Gaussian 16 Rev C01, (2016).
  • [16] Bourne P.E., Beran B., Bi C., Bluhm W.F., Dimitropoulos D., Feng Z., Goodsell D.S., Prlić A., B. Quinn G., W. Rose P., The evolution of the RCSB Protein Data Bank website, Wiley Interdiscip. Rev. Comput. Mol. Sci., 1 (5) (2011) 782-789.
  • [17] Pettersen E.F., Goddard T.D., Huang C.C., Couch G.S., Greenblatt D.M., Meng E.C., Ferrin T.E., UCSF Chimera—a visualization system for exploratory research and analysis, J. Comput. Chem., 25 (13) (2004) 1605-1612.
  • [18] Vidal-Limon A., Aguilar-Toala J.E., Liceaga A.M., Integration of molecular docking analysis and molecular dynamics simulations for studying food proteins and bioactive peptides, J. Agric. Food Chem., 70 (4) (2022) 934-943.
  • [19] Jo S., Vargyas M., Vasko-Szedlar J., Roux B., Im W., PBEQ-Solver for online visualization of electrostatic potential of biomolecules, Nucleic Acids Res., 36 (suppl_2) (2008) W270-W275.
  • [20] Bugnon M., Goullieux M., Röhrig U.F., Perez M.A., Daina A., Michielin O., Zoete., SwissParam 2023: A Modern Web-Based Tool for Efficient Small Molecule Parametrization, J Chem Inf Model ., 63 (21) (2023) 6469-6475.
  • [21] Bulat F.A., Murray J.S., Politzer P., Identifying the most energetic electrons in a molecule: The highest occupied molecular orbital and the average local ionization energy, Comput Theor Chem., 1199 (2021) 113192.
  • [22] Traxler P., Furet P.,. Strategies toward the design of novel and selective protein tyrosine kinase inhibitors, Pharmacology & Therapeutics, 82(2-3) (1999) 195-206.
  • [23] Iwaloye O., Elekofehinti O. O., Olawale F., Chukwuemeka P. O., Kikiowo B., Folorunso I. M., Fragment-based drug design, 2D-QSAR and DFT calculation: Scaffolds of 1, 2, 4, triazolo [1, 5-a] pyrimidin-7-amines as potential inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase, Lett Drug Des Discov., 20(3) (2023) 317-334.
  • [24] Lipinski C.A., Lombardo F., Dominy B.W., Feeney P.J., Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings, Adv. Drug Deliv. Rev., 64 (2012) 4-17.
  • [25] Ibrahim M.T., Uzairu A., Shallangwa G.A., Uba S., Structure-based design of some quinazoline derivatives as epidermal growth factor receptor inhibitors, Egypt. J. Med. Hum. Genet., 21 (2020) 1-12.
  • [26] Clark D.E., In silico prediction of blood–brain barrier permeation, Drug Discov. Today, 8 (20) (2003) 927-933.
  • [27] Zhou S.-F., Xue C.C., Yu X.-Q., Li C., Wang G., Clinically important drug interactions potentially involving mechanism-based inhibition of cytochrome P450 3A4 and the role of therapeutic drug monitoring, Ther. Drug Monit., 29 (6) (2007) 687-710.
  • [28] Loganathan T., Barathinivas A., Soorya C., Balamurugan S., Nagajothi T., Ramya S., Jayakumararaj R., Therapeutics, Physicochemical, Druggable, ADMET Pharmacoinformatics and Therapeutic Potentials of Azadirachtin-a Prenol Lipid (Triterpenoid) from Seed Oil Extracts of Azadirachta indica A. Juss, J. Drug Deliv., 11 (5) (2021) 33-46.
  • [29] Zaki M.E., Al-Hussain S.A., Masand V.H., Akasapu S., Bajaj S.O., El-Sayed N.N., Ghosh A., Lewaa I., Identification of anti-SARS-CoV-2 compounds from food using QSAR-based virtual screening, molecular docking, and molecular dynamics simulation analysis, Pharm., 14(4) (2021) 357.

Year 2024, , 274 - 281, 30.06.2024

Alpaslan Bayrakdar

https://doi.org/10.17776/csj.1410033

Abstract

References

  • [1] Jemal A., Bray F., Center M.M., Ferlay J., Ward E., Forman D., Global cancer statistics, CA Cancer J. Clin., 61 (2) (2011) 69-90.
  • [2] Shang D., Sun D., Shi C., Xu J., Shen M., Hu X., Liu H., Tu Z., Activation of epidermal growth factor receptor signaling mediates cellular senescence induced by certain pro‐inflammatory cytokines, Aging Cell, 19 (5) (2020) e13145.
  • [3] Ukirde R., Sawant R., Nerkar A., Role of Epidermal Growth Factor Receptor Inhibitors in Treating Cancer, Curr Trends Pharm Pharm Chem, 2 (1) (2020) 57-63.
  • [4] Stamos J., Sliwkowski M.X., Eigenbrot C., Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor, J. Biol. Chem., 277 (48) (2002) 46265-46272.
  • [5] Cordover E., Minden A., Lehman S., Zhao O., Signaling pathways downstream to receptor tyrosine kinases: Targets for cancer treatment, J. Cancer Metastatis Treat., 2020 (2020) 1-19.
  • [6] Raymond E., Faivre S., Armand J.P., Epidermal growth factor receptor tyrosine kinase as a target for anticancer therapy, Drugs, 60 (2000) 15-23.
  • [7] Ahmad, A. A., Hussain, K., Shah, M. R., Ashhad Halimi, S. M., Rabbi, F., Ahmad, Z., Khan, I., Rauf, A., Alshammari, A., Rasul Suleria, H. A. (2023). Molecular Insights into the In Vivo Analgesic and Anti-Inflammatory Activity of Indomethacin Analogues, ACS Omega, 8(33), 30048-30056.
  • [8] Das A.J., Das M.K., Singh S.P., Saikia P.P., Singh N., Islam J., Ansari A., Chattopadhyay P., Rajamani P., Miyaji T., Synthesis of salicylic acid phenylethyl ester (SAPE) and its implication in immunomodulatory and anticancer roles, Sci. Rep., 12(1) (2022) 8735.
  • [9] Thiruchenthooran V., Sánchez-López E., Gliszczyńska A., Perspectives of the application of non-steroidal anti-inflammatory drugs in cancer therapy: Attempts to overcome their unfavorable side effects, Cancers, 15 (2) (2023) 475.
  • [10] Ramos-Inza S., Ruberte A.C., Sanmartin C., Sharma A.K., Plano D., NSAIDs: Old Acquaintance in the Pipeline for Cancer Treatment and Prevention─ Structural Modulation, Mechanisms of Action, and Bright Future, J. Med. Chem., 64(22) (2021) 16380-16421.
  • [11] Mohamed-Ezzat R.A., Kariuki B.M., Srour A.M., Synthesis, crystal structure and in vitro anti-proliferative activity of 2-[(4-acetylphenyl) carbamoyl] phenyl acetate, Acta Cryst. E, 79 (11) (2023).
  • [12] Ibrahim M.T., Uzairu A., Shallangwa G.A., Uba S., Structure-based design and activity modeling of novel epidermal growth factor receptor kinase inhibitors; an in silico approach, Sci. Afr., 9 (2020) e00503.
  • [13] Lin S.-Y., Chang Hsu Y., Peng Y.-H., Ke Y.-Y., Lin W.-H., Sun H.-Y., Shiao H.-Y., Kuo F.-M., Chen P.-Y., Lien T.-W., Discovery of a furanopyrimidine-based epidermal growth factor receptor inhibitor (DBPR112) as a clinical candidate for the treatment of non-small cell lung cancer, J. Med. Chem., 62 (22) (2019) 10108-10123.
  • [14] GaussView V., 6.1, R. Dennington, T.A. Keith, J.M. Millam, Semichem Inc, (2016).
  • [15] Frisch M., Trucks G., Schlegel H., Scuseria G., Robb M., Cheeseman J., Scalmani G., Barone V., Petersson G., Nakatsuji H., Gaussian 16 Rev. C. 01, Gaussian 16 Rev C01, (2016).
  • [16] Bourne P.E., Beran B., Bi C., Bluhm W.F., Dimitropoulos D., Feng Z., Goodsell D.S., Prlić A., B. Quinn G., W. Rose P., The evolution of the RCSB Protein Data Bank website, Wiley Interdiscip. Rev. Comput. Mol. Sci., 1 (5) (2011) 782-789.
  • [17] Pettersen E.F., Goddard T.D., Huang C.C., Couch G.S., Greenblatt D.M., Meng E.C., Ferrin T.E., UCSF Chimera—a visualization system for exploratory research and analysis, J. Comput. Chem., 25 (13) (2004) 1605-1612.
  • [18] Vidal-Limon A., Aguilar-Toala J.E., Liceaga A.M., Integration of molecular docking analysis and molecular dynamics simulations for studying food proteins and bioactive peptides, J. Agric. Food Chem., 70 (4) (2022) 934-943.
  • [19] Jo S., Vargyas M., Vasko-Szedlar J., Roux B., Im W., PBEQ-Solver for online visualization of electrostatic potential of biomolecules, Nucleic Acids Res., 36 (suppl_2) (2008) W270-W275.
  • [20] Bugnon M., Goullieux M., Röhrig U.F., Perez M.A., Daina A., Michielin O., Zoete., SwissParam 2023: A Modern Web-Based Tool for Efficient Small Molecule Parametrization, J Chem Inf Model ., 63 (21) (2023) 6469-6475.
  • [21] Bulat F.A., Murray J.S., Politzer P., Identifying the most energetic electrons in a molecule: The highest occupied molecular orbital and the average local ionization energy, Comput Theor Chem., 1199 (2021) 113192.
  • [22] Traxler P., Furet P.,. Strategies toward the design of novel and selective protein tyrosine kinase inhibitors, Pharmacology & Therapeutics, 82(2-3) (1999) 195-206.
  • [23] Iwaloye O., Elekofehinti O. O., Olawale F., Chukwuemeka P. O., Kikiowo B., Folorunso I. M., Fragment-based drug design, 2D-QSAR and DFT calculation: Scaffolds of 1, 2, 4, triazolo [1, 5-a] pyrimidin-7-amines as potential inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase, Lett Drug Des Discov., 20(3) (2023) 317-334.
  • [24] Lipinski C.A., Lombardo F., Dominy B.W., Feeney P.J., Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings, Adv. Drug Deliv. Rev., 64 (2012) 4-17.
  • [25] Ibrahim M.T., Uzairu A., Shallangwa G.A., Uba S., Structure-based design of some quinazoline derivatives as epidermal growth factor receptor inhibitors, Egypt. J. Med. Hum. Genet., 21 (2020) 1-12.
  • [26] Clark D.E., In silico prediction of blood–brain barrier permeation, Drug Discov. Today, 8 (20) (2003) 927-933.
  • [27] Zhou S.-F., Xue C.C., Yu X.-Q., Li C., Wang G., Clinically important drug interactions potentially involving mechanism-based inhibition of cytochrome P450 3A4 and the role of therapeutic drug monitoring, Ther. Drug Monit., 29 (6) (2007) 687-710.
  • [28] Loganathan T., Barathinivas A., Soorya C., Balamurugan S., Nagajothi T., Ramya S., Jayakumararaj R., Therapeutics, Physicochemical, Druggable, ADMET Pharmacoinformatics and Therapeutic Potentials of Azadirachtin-a Prenol Lipid (Triterpenoid) from Seed Oil Extracts of Azadirachta indica A. Juss, J. Drug Deliv., 11 (5) (2021) 33-46.
  • [29] Zaki M.E., Al-Hussain S.A., Masand V.H., Akasapu S., Bajaj S.O., El-Sayed N.N., Ghosh A., Lewaa I., Identification of anti-SARS-CoV-2 compounds from food using QSAR-based virtual screening, molecular docking, and molecular dynamics simulation analysis, Pharm., 14(4) (2021) 357.
There are 29 citations in total.

Details

Primary Language English
Subjects Pharmaceutical Chemistry, Atomic and Molecular Physics
Journal Section Natural Sciences
Authors

Alpaslan Bayrakdar 0000-0001-7967-2245

Publication Date June 30, 2024
Submission Date December 26, 2023
Acceptance Date June 6, 2024
Published in Issue Year 2024

Cite

APA Bayrakdar, A. (2024). In Silico Studies of a Novel Scaffold of Acetylsalicylic Acid Derivatives Against EGFR by Molecular Docking and Molecular Dynamics Simulations. Cumhuriyet Science Journal, 45(2), 274-281. https://doi.org/10.17776/csj.1410033