Article Sidebar

Download
PDF

Main Article Content

Abstract

Herein, we report the synthesis methodology and anticancer evaluation of 15 compounds using copper(I)-catalyzed azide alkyne cycloaddition (CuAAC) to develop a library of saccharin-1,2,3-triazole hybrid molecules. All library compounds showed interactions with various amino acids via the basic sulphonamide and amide linkage of the parental saccharin core motif. Molecular docking studies indicated that alternative positions of saccharin-1,2,3-triazole hybrid molecules added a diversity to the potential hydrogen bonding interactions of these compounds with various amino acids. Present results revealed that hybrid derivatives of saccharin which was prepared from saccharin azide was high yield using CuAAC approach. The compounds showed a moderate anti-cancer activity against SK-OV-3 ovarian cancer cell line and could be considered for the development of potential anticancer drugs based on these new molecules.

Keywords

Saccharine Substituted triazoles Copper(I) Anti-cancer screening Molecular docking Click chemistry.

Article Details

License

Copyright (c) 2020 Asian Journal of Organic & Medicinal Chemistry

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

How to Cite
D. Pambhar, K., M. Khedkar, V., D. Chodvadiya, V., P. Dhamsaniya, A., K. Shah, A., & C. Khunt, R. (2020). Synthesis, Anti-Cancer Screening and Molecular Docking of Saccharine-Triazole Hybrid Molecules using Copper(I) Catalyzed Click Chemistry. Asian Journal of Organic & Medicinal Chemistry, 5(1), 68–76. https://doi.org/10.14233/ajomc.2020.AJOMC-P246
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX

References

  1. B. Meunier, Hybrid Molecules with a Dual Mode of Action: Dream or Reality?, Acc. Chem. Res., 41, 69 (2008); https://doi.org/10.1021/ar7000843
  2. F. Himo, T. Lovell, R. Hilgraf, V.V. Rostovtsev, L. Noodleman, K.B. Sharpless and V.V. Fokin, Copper(I)-Catalyzed Synthesis of Azoles. DFT Study Predicts Unprecedented Reactivity and Intermediates, J. Am. Chem. Soc., 127, 210 (2005); https://doi.org/10.1021/ja0471525
  3. A.L. Garner, cat-ELCCA: Catalyzing Drug Discovery through Click Chemistry, Chem. Commun., 54, 6531 (2018); https://doi.org/10.1039/C8CC02332H
  4. P. Thirumurugan, D. Matosiuk and K. Jozwiak, Click Chemistry for Drug Development and Diverse Chemical-Biology Applications, Chem. Rev., 113, 4905 (2013); https://doi.org/10.1021/cr200409f
  5. J. Huo, H. Hu, M. Zhang, X. Hu, M. Chen, D. Chen, J. Liu, G. Xiao, Y. Wang and Z. Wen, A Mini Review of the Synthesis of Poly-1,2,3-triazole-Based Functional Materials, RSC Adv., 7, 2281 (2017); https://doi.org/10.1039/C6RA27012C
  6. D. Pasini, The Click Reaction as an Efficient Tool for the Construction of Macrocyclic Structures, Molecules, 18, 9512 (2013); https://doi.org/10.3390/molecules18089512
  7. M.-H. Hu, X. Chen, S.-B. Chen, T.-M. Ou, M. Yao, L.-Q. Gu, Z.-S. Huang and J.-H, Tan, A New Application of Click Chemistry in situ: Development of Fluorescent Probe for Specific G-quadruplex Topology, Sci. Rep., 5, 17202 (2015); https://doi.org/10.1038/srep17202
  8. J.P. Meyer, P. Adumeau, J.S. Lewis and B.M. Zeglis, Click Chemistry and Radiochemistry: The First 10 Years, Bioconjug. Chem., 27, 2791 (2016); https://doi.org/10.1021/acs.bioconjchem.6b00561
  9. B. Kahveci, F. Yilmaz, E. Mentese and S. Ülker, Design, Synthesis, and Biological Evaluation of Coumarin-Triazole Hybrid Molecules as Potential Antitumor and Pancreatic Lipase Agents, Arch. Pharm., 350, 1600369 (2017); https://doi.org/10.1002/ardp.201600369
  10. M.H. Shaikh, D.D. Subhedar, F.A.K. Khan, J.N. Sangshetti and B.B. Shingate, 1,2,3-Triazole Incorporated Coumarin Derivatives as Potential Antifungal and Antioxidant Agents, Chin. Chem. Lett., 27, 295 (2016); https://doi.org/10.1016/j.cclet.2015.11.003
  11. L. Han, L. Wang, X. Hou, H. Fu, W. Song, W. Tang and H. Fang, Design, synthesis and Preliminary Bioactivity Studies of 1,2-Dihydrobenzo[d]-isothiazol-3-one-1,1-dioxide Hydroxamic Acid Derivatives as Novel Histone Deacetylase Inhibitors, Bioorg. Med. Chem., 22, 1529 (2014); https://doi.org/10.1016/j.bmc.2014.01.045
  12. M. D’Ascenzio, S. Carradori, C. De Monte, D. Secci, M. Ceruso and C.T. Supuran, Design, Synthesis and Evaluation of N-Substituted Saccharin Derivatives as Selective Inhibitors of Tumor-associated Carbonic Anhydrase XII, Bioorg. Med. Chem., 22, 1821 (2014); https://doi.org/10.1016/j.bmc.2014.01.056
  13. M.S.A. Elsayed, M.E. El-Araby, R.A.T. Serya, A.H. El-Khatib, M.W. Linscheid and K.A.M. Abouzid, Structure-Based Design and Synthesis of Novel Pseudosaccharine Derivatives as Antiproliferative Agents and Kinase Inhibitors, Eur. J. Med. Chem., 61, 122 (2013); https://doi.org/10.1016/j.ejmech.2012.09.039
  14. K.D. Combrink, H.B. Gulgeze, N.A. Meanwell, B.C. Pearce, P. Zulan, G.S. Bisacchi, D.G.M. Roberts, P. Stanley and S.M. Seiler, 1,2-Benziso-thiazol-3-one 1,1-Dioxide Inhibitors of Human Mast Cell Tryptase, J. Med. Chem., 41, 4854 (1998); https://doi.org/10.1021/jm9804580
  15. N. Gençer, D. Demir, F. Sonmez and M. Kucukislamoglu, New Saccharin Derivatives as Tyrosinase Inhibitors, Bioorg. Med. Chem., 20, 2811 (2012); https://doi.org/10.1016/j.bmc.2012.03.033
  16. M.A. Patane, R.M. DiPardo, R.A.P. Price, R.S.L. Chang, R.W. Ransom, S.S. O’Malley, J.D. Salvo and M.G. Bock, Selective a-1A Adrenergic Receptor Antagonists. Effects of Pharmacophore Regio- and Stereo-chemistry on Potency and Selectivity, Bioorg. Med. Chem. Lett., 8, 2495 (1998); https://doi.org/10.1016/S0960-894X(98)00451-X
  17. C.E. Sunkel, M. Fau de Casa-Juana, F.J. Cillero, J.G. Priego and M.P. Ortega, Synthesis, Platelet Aggregation Inhibitory Activity, and in vivo Antithrombotic Activity of New 1,4-dihydropyridines, J. Med. Chem., 31, 1886 (1988); https://doi.org/10.1021/jm00118a004
  18. H. Sommermeyer, R. Schreiber, J.M. Greuel, J. De Vry and T. Glaser, Anxiolytic Effects of the 5-HT1A Receptor Agonist Ipsapirone in the Rat: Neurobiological Correlates, Eur. J. Pharmacol., 240, 29 (1993); https://doi.org/10.1016/0014-2999(93)90541-O
  19. J. Blanchet, T. Macklin, P. Ang, C. Metallinos and V. Snieckus, Directed Ortho Metalation-Cross Coupling Strategies. N-Cumyl Arylsulfonamides. Facile Deprotection and Expedient Route to 7- and 4,7-Substituted Saccharins, J. Org. Chem., 72, 3199 (2007); https://doi.org/10.1021/jo062385v
  20. M.B. Youdim and R. Ashkenazi, Serotonergic Involvement in Pharma-cological Action of Anxiolytic- Sedatives Thalidomide and Supidimide, Eur. J. Pharmacol., 119, 39 (1985); https://doi.org/10.1016/0014-2999(85)90319-X
  21. T. Ueda, H. Konishi and K. Manabe, Palladium-Catalyzed Reductive Carbonylation of Aryl Halides with N-Formylsaccharin as a CO Source, Angew. Chem. Int. Ed., 52, 8611 (2013); https://doi.org/10.1002/anie.201303926
  22. T. Cochet, V. Bellosta, A. Greiner, D. Roche and J. Cossy, N-Formylsaccharin: A New Formylating Agent, Synlett, 1920 (2011); https://doi.org/10.1055/s-0030-1260951
  23. R.A. Friesner, J.L. Banks, R.B. Murphy, T.A. Halgren, J.J. Klicic, D.T. Mainz, M.P. Repasky, E.H. Knoll, M. Shelley, J.K. Perry, D.E. Shaw, P. Francis and P.S. Shenkin, Glide: A New Approach for Rapid, Accurate Docking and Scoring. 1. Method and Assessment of Docking Accuracy, J. Med. Chem., 47, 1739 (2004); https://doi.org/10.1021/jm0306430
  24. T.A. Halgren, R.B. Murphy, R.A. Friesner, H.S. Beard, L.L. Frye, W.T. Pollard and J.L. Banks, Glide: A New Approach for Rapid, Accurate Docking and Scoring. 2. Enrichment Factors in Database Screening, J. Med. Chem., 47, 1750 (2004); https://doi.org/10.1021/jm030644s