Article Sidebar

Download
PDF

Main Article Content

Abstract

Novel 4-{3-[2-(2-morpholin-4-yl-ethoxy)phenyl]-5-phenyl-pyrazol-1-yl}benzenesulfonamide (7) was synthesized and evaluated for its anti-breast cancer activity. It was prepared by cyclocondensation reaction of morpholine-substituted β-diketone, 1-[2-(2-morpholin-4-yl-ethoxy)-phenyl]-3-phenyl-propane-1,3-dione (3) with 4-hydrazinobenzene-sulfonamide hydrochloride (6). Chemical structure of titled compound (7) was confirmed by FTIR, 1H & 13C NMR and HRMS spectroscoic analyses. The anticancer activity of titled compound 7 was evaluated against MCF-7 breast cancer cell line by MTT assay. Molecular docking was performed to predict its plausible binding with the estrogen receptor α(ERα) using Molecular Operating Environment 2019.0101 software. The MTT assay results showed that titled compound 7 exhibited better anticancer activity against MCF7 cells (IC50: 4.25 μM) than standard drug, 4-hydroxytamoxifen (IC50: 8.22 μM). Results of molecular docking studies were found in good agreement with the results of anticancer evaluation, as the binding score of titled compound 7 (-16.9872 kcal/mol) was lower as compared to 4-hydroxytamoxifen (-15.1112 kcal/mol). The new cationic interaction of titled compound 7 with Trp383 and hydrogen bonding interaction with Phe404 in active site of ERα made its anticancer activity better than 4-hydroxytamoxifen. Thus, 4-{3-[2-(2-morpholin-4-yl-ethoxy)phenyl]-5-phenyl-pyrazol-1-yl}benzenesulfonamide (7) was emerged as a potent anti-breast cancer agent.

Keywords

Celecoxib Benzenesulfonamide derivative Molecular docking anti-breast cancer agent

Article Details

How to Cite
Kumar, P., Prakash Kumar, J., Barnwal, J., & Singh, R. (2020). Design, Synthesis and Molecular Docking Studies of 4-{3-[2-(2-Morpholin-4-yl-ethoxy)phenyl]-5-phenyl-pyrazol-1-yl}-benzenesulfonamide as Anti-Breast Cancer Agent. Asian Journal of Organic & Medicinal Chemistry, 5(4), 301–306. https://doi.org/10.14233/ajomc.2020.AJOMC-P271
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX

References

  1. American Cancer Society, Breast Cancer Facts and Figures 2019-2020, Atlanta, American Cancer Society, Inc. (2019).
  2. B.S. Katzenellenbogen and J.A. Katzenellenbogen, Estrogen Receptor Transcription and Transactivation Estrogen Receptor Alpha and Estrogen Receptor Beta: Regulation by Selective Estrogen Receptor Modulators and Importance in Breast Cancer, Breast Cancer Res., 2, 335 (2000); https://doi.org/10.1186/bcr78
  3. K. Brown, Breast Cancer Chemoprevention: Risk-Benefit Effects of the Antioestrogen Tamoxifen, Expert Opin. Drug Saf., 1, 253 (2002); https://doi.org/10.1517/14740338.1.3.253
  4. N.J. Thumar and M.P. Patel, Synthesis, Characterization and Antimicro-bial Evaluation of Carbostyril Derivatives of 1H-Pyrazole, Saudi Pharm. J., 19, 75 (2011); https://doi.org/10.1016/j.jsps.2011.01.005
  5. A. Ansari, A. Ali, M. Asif and Shamsuzzaman, Review: Biologically Active Pyrazole Derivatives, New J. Chem., 41, 16 (2017); https://doi.org/10.1039/C6NJ03181A
  6. V. Kumar, K. Kaur, G.K. Gupta, A.K. Gupta and S. Kumar, Developments in Synthesis of the Anti-inflammatory Drug, Celecoxib: A Review, Recent Pat. Inflamm. Allergy Drug Discov., 7, 124 (2013); https://doi.org/10.2174/1872213X11307020004
  7. R. Zaninetti, S.V. Cortese, S. Aprile, A. Massarotti, P.L. Canonico, G. Sorba, G. Grosa, A.A. Genazzani and T. Pirali, A Concise Synthesis of Pyrazole Analogues of Combretastatin A1 as Potent Anti-Tubulin Agents, ChemMedChem, 8, 633 (2013); https://doi.org/10.1002/cmdc.201200561
  8. T. Padmini and B.R. Kamal, Synthesis, Anti-inflammatory, Analgesic and Antipyretic Activity of Novel 1,3,5-Trisubstituted Pyrazole Derivatives, Asian J. Chem., 31, 1225 (2019); https://doi.org/10.14233/ajchem.2019.21781
  9. A. Zamri, H.Y. Teruna, S. Wulansari, N. Herfindo, N. Frimayanti and I. Ikhtiarudin, 3-(3,4-Dimethoxyphenyl)-5-(2-fluorophenyl)-1-phenyl-4,5-dihydro-1H-pyrazole, Molbank, 2019, M1088 (2019); https://doi.org/10.3390/M1088
  10. N. Nakamichi, Y. Kawashita and M. Hayashi, Oxidative Aromatization of 1,3,5-Trisubstituted Pyrazolines and Hantzsch 1,4-Dihydropyridines by Pd/C in Acetic Acid, Org. Lett., 4, 3955 (2002); https://doi.org/10.1021/ol0268135
  11. K. Karrouchi, S. Radi, Y. Ramli, J. Taoufik, Y.N. Mabkhot, F.A. Al-Aizari and M. Ansar, Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review, Molecules, 23, 134 (2018); https://doi.org/10.3390/molecules23010134
  12. D.C. Liu, M.J. Gao, Q. Huo, T. Ma, Y. Wang and C.Z. Wu, Design, Synthesis, and Apoptosis-Promoting Effect Evaluation of Novel Pyrazole with Benzo[d]Thiazole Derivatives Containing Aminoguanidine Units, J. Enzyme Inhib. Med. Chem., 34, 829 (2019); https://doi.org/10.1080/14756366.2019.1591391
  13. A.B. Shaik, G.K. Rao, G.B. Kumar, N. Patel, V.S. Reddy, I. Khan, S.R. Routhu, C.G. Kumar, I. Veena, K. Chandra Shekar, M. Barkume, S. Jadhav, A. Juvekar, J. Kode, M. Pal-Bhadra and A. Kamal, Design, Synthesis and Biological Evaluation of Novel Pyrazolochalcones as Potential Modulators of PI3K/Akt/mTOR Pathway and Inducers of Apoptosis in Breast Cancer Cells, Eur. J. Med. Chem., 139, 305 (2017); https://doi.org/10.1016/j.ejmech.2017.07.056
  14. N.M.H. Khalifa and M.A. Al-Omar, Substituted Pyrazole Derivatives, US Patent 10039749B1 (2018).
  15. D. Gao, A.J. Hlinak, A.M. Mazhary, J.E. Truelove and M.B.W. Vaughn, Celecoxib Compositions, Patent WO2000032189A1 (2000).
  16. Z.J. Dai, X.B. Ma, H.F. Kang, J. Gao, W.L. Min, H.T. Guan, Y. Diao, W.F. Lu and X.J. Wang, Antitumor Activity of the Selective Cyclo-oxygenase-2 Inhibitor, Celecoxib, on Breast Cancer in vitro and in vivo, Cancer Cell Int., 12, 53 (2012); https://doi.org/10.1186/1475-2867-12-53
  17. L.L. Winfield and F. Payton-Stewart, Celecoxib and Bcl-2: Emerging Possibilities for Anticancer Drug Design, Future Med. Chem., 4, 361 (2012); https://doi.org/10.4155/fmc.11.177
  18. J. Feng, H. Qi, X. Sun, S. Feng, Z. Liu, Y. Song and X. Qiao, Synthesis of Novel Pyrazole Derivatives as Promising DNA-Binding Agents and Evaluation of Antitumor and Antitopoisomerases I/II Activities, Chem. Pharm. Bull. (Tokyo), 66, 1065 (2018); https://doi.org/10.1248/cpb.c18-00546
  19. M.K. Gurjar, N. Kaliaperumal, P.P. Ahirrao, R. Baireddy, S. Nandala, P. Balasubramanian, P.P. Panchabhai and S.S. Mehta, Process for Preparation of Aolmitriptan, US Patent 9006453B2 (2015).
  20. M.S. Smyth and J.H. Martin, X-Ray Crystallography, Mol. Pathol., 53, 8 (2000); https://doi.org/10.1136/mp.53.1.8
  21. D. Plewczynski, M. Laz'niewski, R. Augustyniak and K. Ginalski, Can We Trust Docking Results? Evaluation of Seven Commonly used Programs on PDBbind Database, J. Comput. Chem., 32, 742 (2011); https://doi.org/10.1002/jcc.21643
  22. R. Prasetiawati, A. Zamri, M.I. Barliana and M. Muchtaridi, in silico Predictive for Modification of Chalcone with Pyrazole Derivatives as a Novel Therapeutic Compound for Targeted Breast Cancer Treatment, J. Appl. Pharm. Sci., 9, 20 (2019); https://doi.org/10.7324/JAPS.2019.90203
  23. M. Muchtaridi, H.N. Syahidah, A. Subarnas, M. Yusuf, S.D. Bryant and T. Langer, Molecular Docking and 3D-Pharmacophore Modeling to Study the Interactions of Chalcone Derivatives with Estrogen Receptor Alpha, Pharmaceuticals, 10, 81 (2017); https://doi.org/10.3390/ph10040081