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Design, Synthesis and Cytotoxicity Evaluation of Structural Analogues of Imatinib

Received: 28 February 2017     Accepted: 21 April 2017     Published: 19 May 2017
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Abstract

Several novel imatinib structure analogues were synthesized. Antiproliferative activity testing on various leukemic cell lines showed 1-2 fold less activity against K562 cells compared to imatinib. Autodock Vina’s docking studies predicted no differences in binding affinity of the titled compounds while positive relationship between activity and calculated lipophilicity was found. Further imatinib structure optimization pathways were evaluated.

Published in Journal of Drug Design and Medicinal Chemistry (Volume 3, Issue 2)
DOI 10.11648/j.jddmc.20170302.12
Page(s) 27-31
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2017. Published by Science Publishing Group

Keywords

Imatinib, Structural Analogues, Protein Kinase Inhibitor, Molecule Design, Anticancer

References
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[2] T. G. Lugo, A. M. Pendergast, A. J. Muller, O. N. Witte, “Tyrosine kinase activity and transformation potency of bcr-abl oncogene products”, Science, vol. 247, pp. 1079-1082, 1990.
[3] M. Baccarani, F. Castagnetti, G. Gugliotta, G. Rosti, “A review of the European LeukemiaNet recommendations for the management of CML”, Ann. Hematol., vol. 94, suppl. 2, pp. 141-147, 2015.
[4] M. J. Eck, P. W. Manley. “The Interplay of Structural Information and Functional Studies in Kinase Drug Design: Insights from BCR-Abl.” Current Opinion in Cell Biology, vol. 21.2, pp. 288–295, 2009.
[5] F. Lee, A. Fandi, M. Voi, “Overcoming kinase resistance in chronic myeloid leukemia”, Int. J. Biochem. Cell Biol, vol. 40(3), pp: 334-343, 2008.
[6] V. E. Agabekov, et al. “Preparation of 4-[(4-methyl-1-pyperazinil)-methyl]-N-[4-methyl-3-{[4-(3-pyridyl)-2-pyrimidinyl]-amino}phenyl]benzamide sulfonate”, pat. 17047, Rep. of Belarus, 30.04.2013.
[7] H. G. Jørgensen, E. K. Allan, N. E. Jordanides, J. C. Mountford, T. L. Holyoake, Allan “Nilotinib exerts equipotent antiproliferative effects to imatinib and does not induce apoptosis in CD34+ CML cells”, Blood, vol. 109(9), pp 4016-4019, 2007.
[8] O. Trott, A. J. Olson, “AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading”, J. Comp. Chem., vol. 31, pp. 455-461, 2010.
[9] https://cactus.nci.nih.gov/translate/
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[11] N. M. O'Boyle, M. Banck, C. A. James, C. Morley, T. Vandermeersch, G. R. Hutchison, Open Babel: An open chemical toolbox", J. Cheminf., 3: 33, 2011.
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  • APA Style

    Aliaksandr Faryna, Elena Kalinichenko, Olga Avdoshko, Alla Belko. (2017). Design, Synthesis and Cytotoxicity Evaluation of Structural Analogues of Imatinib. Journal of Drug Design and Medicinal Chemistry, 3(2), 27-31. https://doi.org/10.11648/j.jddmc.20170302.12

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    ACS Style

    Aliaksandr Faryna; Elena Kalinichenko; Olga Avdoshko; Alla Belko. Design, Synthesis and Cytotoxicity Evaluation of Structural Analogues of Imatinib. J. Drug Des. Med. Chem. 2017, 3(2), 27-31. doi: 10.11648/j.jddmc.20170302.12

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    AMA Style

    Aliaksandr Faryna, Elena Kalinichenko, Olga Avdoshko, Alla Belko. Design, Synthesis and Cytotoxicity Evaluation of Structural Analogues of Imatinib. J Drug Des Med Chem. 2017;3(2):27-31. doi: 10.11648/j.jddmc.20170302.12

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  • @article{10.11648/j.jddmc.20170302.12,
      author = {Aliaksandr Faryna and Elena Kalinichenko and Olga Avdoshko and Alla Belko},
      title = {Design, Synthesis and Cytotoxicity Evaluation of Structural Analogues of Imatinib},
      journal = {Journal of Drug Design and Medicinal Chemistry},
      volume = {3},
      number = {2},
      pages = {27-31},
      doi = {10.11648/j.jddmc.20170302.12},
      url = {https://doi.org/10.11648/j.jddmc.20170302.12},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.jddmc.20170302.12},
      abstract = {Several novel imatinib structure analogues were synthesized. Antiproliferative activity testing on various leukemic cell lines showed 1-2 fold less activity against K562 cells compared to imatinib. Autodock Vina’s docking studies predicted no differences in binding affinity of the titled compounds while positive relationship between activity and calculated lipophilicity was found. Further imatinib structure optimization pathways were evaluated.},
     year = {2017}
    }
    

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    T1  - Design, Synthesis and Cytotoxicity Evaluation of Structural Analogues of Imatinib
    AU  - Aliaksandr Faryna
    AU  - Elena Kalinichenko
    AU  - Olga Avdoshko
    AU  - Alla Belko
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    DO  - 10.11648/j.jddmc.20170302.12
    T2  - Journal of Drug Design and Medicinal Chemistry
    JF  - Journal of Drug Design and Medicinal Chemistry
    JO  - Journal of Drug Design and Medicinal Chemistry
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    PB  - Science Publishing Group
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    UR  - https://doi.org/10.11648/j.jddmc.20170302.12
    AB  - Several novel imatinib structure analogues were synthesized. Antiproliferative activity testing on various leukemic cell lines showed 1-2 fold less activity against K562 cells compared to imatinib. Autodock Vina’s docking studies predicted no differences in binding affinity of the titled compounds while positive relationship between activity and calculated lipophilicity was found. Further imatinib structure optimization pathways were evaluated.
    VL  - 3
    IS  - 2
    ER  - 

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Author Information
  • Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Minsk, Belarus

  • Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Minsk, Belarus

  • Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Minsk, Belarus

  • Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Minsk, Belarus

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