Evaluation of the Anticancer Potentials of some Quercetin Derivatives - An in Silico Approach

Authors

  • Olorunfemi A. Eseyin, Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, University of Uyo, Uyo, Akwa Ibom State, Nigeria
  • Ekarika Johnson Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, University of Uyo, Uyo, Akwa Ibom State, Nigeria
  • Emmanuel I. Etim Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, University of Uyo, Uyo, Akwa Ibom State, Nigeria
  • Aniefiok Sunday Udobre Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, University of Uyo, Uyo, Akwa Ibom State, Nigeria
  • Aniekan Ebong Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, University of Uyo, Uyo, Akwa Ibom State, Nigeria
  • Paschal Anthony Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, University of Uyo, Uyo, Akwa Ibom State, Nigeria
  • Asanga Edet Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, University of Uyo, Uyo, Akwa Ibom State, Nigeria
  • Etiemana Charles Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, University of Uyo, Uyo, Akwa Ibom State, Nigeria
  • Festus Esenam Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, University of Uyo, Uyo, Akwa Ibom State, Nigeria
  • Victor Attih Department of Pharmaceutical and Medicinal Chemistry, Faculty of Pharmacy, University of Uyo, Uyo, Akwa Ibom State, Nigeria
  • Abayomi E. Omotosho Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, University of Port harcourt, Nigeria
  • Mohammed Lazhari Department of Anesthesiology and Intensive Care, Tripoli University School of Medical Technology, Libya

Keywords:

Quercetin, cancer, molecular docking, in silico

Abstract

Background: Quercetin has been reported to possess anticancer activities. This study was aimed at designing some derivatives of quercetin and evaluating their binding affinities to target proteins implicated in cancer.
Methodology: Derivatives of quercetin were designed with ChemDraw. The targets: Phosphodiesterases (PDEs; 1XMU), Cyclooxygenase-1 (COX-1; 4O1Z); Cyclooxygenase-2 (COX-2; 4M11); Epidermal growth factor receptor (EGFR, 6DUK); α-glucosidase (5KZW); and TNF-α-inducing protein (TNFA, 3VNC) were downloaded from the Protein data bank. Ligands and targets were converted to pdbqt format using PyRx. Carboplatin, carmustine, dacarbazine, dexamethasone, doxorubicin, floxuridine, hydroxyurea, imatinib, lomustine, methotrexate, prednisone, valrubicin and vincristine were used as reference drugs. Molecular docking of the ligands with each of the target proteins was done using Autodock Vina. Discovery Studio was used to visualise ligand-protein binding interactions. Calculated molecular and pharmacokinetic properties were obtained from molinspiration and pKCM websites, respectively.
Results: Ligand 1 (quercetin) had a binding energy of -9.5 kcal/mol. While ligands 10, 39, 34 and 38 had binding energy of -9.6. -9.7, -9.8 and -9.9 kcal/mol, respectively, on PDE. On COX-1 ligand 1 (Quercetin) had a binding energy of -9.8 kcal/mol while ligands 17 and 26 had better binding energy of -10.0 and -10.2 kcal/mol, respectively. On COX-2, the binding energy for ligands 1 (quercetin), 15 and 25 were -10.0, -10.4 and -10.5 kcal/mol, respectively. While binding energy for ligand 1 (quercetin) on EGFR was -8.8 kcal/mol those for ligands 3, 15 and 27 were -9.4 kcal/mol; ligands 37 and 39 were -9.7 kcal/mol. None of the ligands in this study had a better binding energy than quercetin (-7.4 kcal/mol) on TNF. Imatinib and valrubicin had a good binding affinity to all the protein targets.
Conclusion: Some of the derivatives of quercetin (ligands) exhibited better binding affinities to the various cancer target proteins studied in this work. These derivatives have good anticancer potential.

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Published

2023-02-17

How to Cite

A. Eseyin, , O., Johnson, E., I. Etim, E., Sunday Udobre, A., Ebong, A., Anthony, P., Edet, A., Charles, E., Esenam, F., Attih, V., E. Omotosho, A., & Lazhari, M. (2023). Evaluation of the Anticancer Potentials of some Quercetin Derivatives - An in Silico Approach. Journal of Drug Discovery and Research, 1(2), 8–25. Retrieved from https://ddrg.net/index.php/ddrg/article/view/36

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