Document Type: Original Research Article

Authors

1 Research and Development Department, Shari Pharmaceutical Company, Tehran, Iran

2 Department of Science, Islamshahr Branch, Islamic Azad University, Islamshahr, Iran

3 Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

4 Science and Research Branch, Islamic Azad University, Tehran, Iran

5 Physics Department, Faculty of Science, Lorestan University, Khorramabad, Iran

Abstract

Evaluating structural and medicinal properties of novel silicon containing molecules of Ellagic acid (EADC) is the main purpose of this work. Density functional theory (DFT) methods as implemented in the Gaussian 03 program and molecular modeling methods using the Molegro Virtual Docker (MVD) program and SwissADME web server have been employed to achieve the purpose. Here, the molecular structures of original EADC and modified EACS and EADS were optimized at the B3LYP/6-311++G(d,p) level of theory. The reactivity and stability properties of the investigated molecules were evaluated via global reactivity indices using frontier molecular orbitals (FMOs) energies; showing the stability order of the molecules as EADS > EACS > EADC. On the other hand, obtained data from performed molecular docking analyses indicated that the steric interactions play dominant role of molecular binding to VEGFR-2 Kinase enzyme. Furthermore, EACS has been viewed as the strongest interacting molecule with other biomacromolecules. And finally, the evaluated ADME properties indicated that the oral bioavailability for the investigated compounds is low.

Graphical Abstract

Keywords

1. Boyle P, Levin B. World cancer report 2008. IARC Press, International Agency for Research on Cancer; 2008.

2. Ma J, Jemal A, Fedewa SA, Islami F, Lichtenfeld JL, Wender RC, Cullen KJ, Brawley OW. The American Cancer Society 2035 challenge goal on cancer mortality reduction. CA 2019;69:351-362.

3. Zhang HM, Zhao L, Li H, Xu H, Chen WW, Tao L. Research progress on the anticarcinogenic actions and mechanisms of ellagic acid. Cancer Biol. Med. 2014;11:92.

4. Polyak K. Breast cancer: origins and evolution. J. Clin. Invest. 2007;117:3155-3163.

5. Lu J, Steeg PS, Price JE, Krishnamurthy S, Mani SA, Reuben J, Cristofanilli M, Dontu G, Bidaut L, Valero V, Hortobagyi GN. Breast cancer metastasis: Challenges and opportunities. Cancer Res. 2009;69:4951-4953.

6. Ramasamy S, Wahab A, Manickam S, Zakaria Z. Growth inhibition of human gynecologic and colon cancer cells by Phyllanthus watsonii through apoptosis induction. PloS One 2012;7:e34793.

7. Cragg GM, Newman DJ. Plants as a source of anti-cancer agents. J. Ethnopharmacol. 2005;100:72-79.

8. Papoutsi Z, Kassi E, Tsiapara A, Fokialakis N, Chrousos GP, Moutsatsou P. Evaluation of estrogenic/antiestrogenic activity of ellagic acid via the estrogen receptor subtypes ERα and ERβ. J. Agricult. Food Chem. 2005;53:7715-7720.

9. Mohan N, Latha M. insilico docking and interaction analysis of ellagic acid and curcumin derivatives against human cancer. Indian J. Sci. Res. 2018;18:22-28.

10. Ghamsari PA, Samadizadeh M, Mirzaei M. Cytidine derivatives as inhibitors of methyltransferase enzyme. Eurasian Chem. Commun. 2020;2:433-439.

11. Ozkendir OM. Boron activity in metal containing materials. Adv. J. Chem. B 2020;2:48-54.

12. Mirzaei M. Lab-in-Silico. Adv. J. Chem. B 2020;2:1-2.

13. Ariaei S, Basiri H, Ramezani M. Selective adsorption function of B16C16 nano-cage for H2O, CO, CH4 and NO2. Adv. J. Chem. B 2020;2:18-25.

14. Ghanbari N, Azizian H, Mirzaei M. Computational studies of furanone and its 5Methyl/5Phenyl derivatives. Adv. J. Chem. B 2020;2:33-38.

15. Molaeian M, Davood A, Mirzaei M. Non-covalent interactions of N-(4-carboxyphenyl)phthalimide with CNTs. Adv. J. Chem. B 2020;2:39-45.

16. Nabati M, Bodaghi-Namileh V. Molecular Modeling of 3-(1, 3-Dioxoisoindolin-2-yl) benzyl Nitrate and its Molecular Docking Study with Phosphodiesterase-5 (PDE5). Adv. J. Chem. A 2020;3:58-69.

17. Nabati M, Lohrasbi E, Sabahnoo H, Bodaghi-Namileh V, Mazidi M, Mohammadnejad-Mehrabani H, Tavakkoli A, Gervand A. In silico study of metoclopramide as a small molecule of dopamine D2 receptor: a quantum-mechanical (QM) based molecular docking treatment. Chem. Method. 2020;4:19-33.

18. Nabati M. Exploring molecular docking and electronic studies of [11C] LY2795050 as a novel antagonist tracer for positron emission tomography (PET) scan of the kappa (κ) and mu (µ) opioid receptors (KOR and MOR). J. Med. Chem. Sci. 2020;3:22-34.

19. Nabati M, Bodaghi V. In silico study of the active components (17α-ethinyl estradiol and segesterone acetate) of annovera as a novel vaginal contraceptive system by docking of their binding to estrogen and progesterone receptors. Eurasian Chem. Commun. 2020;2:234-246.

20. Samadi Z, Mirzaei M, Hadipour NL, Khorami SA. Density functional calculations of oxygen, nitrogen and hydrogen electric field gradient and chemical shielding tensors to study hydrogen bonding properties of peptide group (OC–NH) in crystalline acetamide. J. Mol. Graph. Model. 2008;26:977-981.

21. Davarpanah M, Abbasi H, Nabati M, Sabahnoo H, Bodaghi-Namileh V, Mazidi M, Movahhed-Tazehkand H, Mohammadnejad-Mehrabani H. Kit formulation of active pharmaceutical ingredient d, l-HMPAO as a brain perfusion diagnostic system. Prog. Chem. Biochem. Res. 2019;2:185-191.

22. Nabati M, Bodaghi-Namileh V. Non-competitive N-methyl-D-aspartate (NMDA) receptor (NR2B) structure in complex with antidepressant arketamine. Iran. J. Org. Chem. 2019;11:2591-2598.

23. Nabati M, Bodaghi-Namileh V, Sarshar S. Molecular modeling of the antagonist compound esketamine and its molecular docking study with non-competitive N-methyl-D-aspartate (NMDA) receptors NR1, NR2A, NR2B and NR2D. Prog. Chem. Biochem. Res. 2019;2: 108-119.

24. Nabati M, Bodaghi-Namileh V. Design of novel drugs (P3TZ, H2P3TZ, M2P3TZ, H4P3TZ and M4P3TZ) based on zonisamide for autism treatment by binding to potassium voltage-gated channel subfamily D member 2 (Kv4. 2). Int. J. New Chem. 2019;6:254-276.

25. Mirzaei M, Mirzaei M. The C-doped AlP nanotubes: A computational study. Solid State Sci. 2011;13:244-250.

26. Behzadi H, Hadipour NL, Mirzaei M. A density functional study of 17O, 14N and 2H electric field gradient tensors in the real crystalline structure of α-glycine. Biophys. Chem. 2007;125:179-183.

27. Nabati M, Sabahnoo H. Spectroscopic (FT-IR and UV-Vis), electronic and docking studies on the red clover isoflavone irilone as a progesterone receptor (PR) effect supporter in endometrial and ovarian cancer cell lines. J. Med. Chem. Sci. 2019;2:118-125.

28. Nabati M. Modeling and interactions analysis of the novel antagonist agent flibanserin with 5-hydroxytryptamine 2A (5-HT2A) serotonin receptor as a HSDD treatment in premenopausal women. Iran. Chem. Commun. 2019;7:324-334.

29. Nabati M, Sabahnoo H, Lohrasbi E, Mazidi M. Structural properties study and spectroscopic (FT-IR and UV-Vis) profiling of the novel antagonist LY2157299 as a transforming growth factor-β (TGF-β) receptor I kinase inhibitor by quantum-mechanical (QM) and molecular docking techniques. Chem. Method. 2019;3:377-391.

30. Nabati M. Insight into the structural  and  spectral  (IR and UV-Vis) properties of the salts of alkali (Li, Na and K) and alkaline earth (Be, Mg and Ca) metals with pertechnetate oxoanion (99mTcO4-) as the convenient water-soluble sources of the radioactive element technetium. Chem. Method. 2019;3:258-270.

31. Nabati M, Bodaghi-Namileh V. Physicochemical properties analysis and dopamine D2 receptor (D2R) docking of zotepine as an atypical antipsychotic antagonist. J. Phys. Theor. Chem. 2018;15:149-157.

32. Nabati M, Bodaghi-Namileh V, Mazidi M. Evaluation of [18F] FPTT Molecular structure and its binding to progesterone receptor (PR) for PET scan of breast cancer receptor (PR) for PET scan of breast cancer. J. Phys. Theor. Chem. 2019;15:159-171.

33. Nabati M, Pournamdari E, Dashti-Rahmatabadi Y, Sarshar S. Withaferin A (WIT) interaction with beta–tubulin to promote tubulin degradation: In silico study. Adv. J. Chem. B 2020;2:26-32.

34. Nabati M, Bodaghi-Namileh V. Design of novel tazarotene derivatives as potential antipsoriatic drugs: physicochemical properties study and molecular docking analysis of their binding to retinoic acid receptor family (RAR-alpha, RAR-beta and RAR-gamma). J. Med. Chem. Sci. 2020;3:162-175.

35. Oguro Y, Miyamoto N, Okada K, Takagi T, Iwata H, Awazu Y, Miki H, Hori A, Kamiyama K, Imamura S. Design, synthesis, and evaluation of 5-methyl-4-phenoxy-5H-pyrrolo [3, 2-d] pyrimidine derivatives: novel VEGFR2 kinase inhibitors binding to inactive kinase conformation. Bioorg. Med. Chem. 2010;18:7260-7273.

36. Nabati M, Sabahnoo H, Bodaghi-Namileh V. Molecular Structure Determination and Stability Parameters Study of 99mTc-MDP (Technetium 99m Methylene Diphosphonate) Cold Kit and Analysis of Its Binding to Osteocalcin Receptor as a Bone Scan Agent. Chem. Method. 2020;4:297-310.

37. Adem S, Eyupoglu V, Sarfraz I, Rasul A, Ali M. Identification of potent COVID-19 main protease (Mpro) inhibitors from natural polyphenols: An in silico strategy unveils a hope against CORONA. Preprints 2020, 2020030333.