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Dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-4-ones as a new class of CK2 inhibitors

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Abstract

Identification of new small molecules inhibiting protein kinase CK2 is highly required for the study of this protein’s functions in cell and for the further development of novel pharmaceuticals against a variety of disorders associated with CK2 activity. In this article, a virtual screening of a random small-molecule library was performed and 12 compounds were initially selected for biochemical tests toward CK2. Among them, the most active compound 1 (\(\hbox {IC}_{50} = 6.8\,\upmu \hbox {M}\)) belonged to dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-4-ones. The complex of this compound with CK2 was analyzed, and key ligand–enzyme interactions were determined. Then, a virtual screening of 231 dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-4-one derivatives was performed and 37 compounds were chosen for in vitro testing. It was found that 32 compounds inhibit CK2 with \(\hbox {IC}_{50}\) values from 2.5 to 7.5 \(\upmu \hbox {M}\). These results demonstrate that dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-4-one is a novel class of CK2 inhibitors.

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Acknowledgements

We thank to Dr. Yana I. Sakhno and Dr. Vitaliy N. Chernenko for granting their substances for this study. Virtual screening and biochemical tests were supported by a Grant from the National Academy of Sciences of Ukraine 10112U004110.

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Authors and Affiliations

  1. Taras Shevchenko National University of Kyiv, 64/13, Volodymyrska Street, Kiev, 01601, Ukraine

    Mykola V. Protopopov

  2. Institute of Molecular Biology and Genetics, NAS of Ukraine, 150 Zabolotnogo Street, Kiev, 03143, Ukraine

    Mykola V. Protopopov, Olga V. Ostrynska, Sergiy A. Starosyla, Volodymyr Bdzhola & Sergiy M. Yarmoluk

  3. Department of Organic and Bioorganic Chemistry, SSI “Institute for Single Crystals” of NAS of Ukraine, 60 Nauky Ave., Kharkiv, 61072, Ukraine

    Maria A. Vodolazhenko, Svetlana M. Sirko, Nikolay Yu. Gorobets & Sergey M. Desenko

  4. Department of Medical and Bioorganic Chemistry, Kharkiv National Medical University, 4 Nauky Ave., Kharkiv, 61022, Ukraine

    Maria A. Vodolazhenko

  5. Department of Organic Chemistry, V. N. Karazin Kharkiv National University, Svobody Sq. 4, Kharkiv, 61077, Ukraine

    Nikolay Yu. Gorobets & Sergey M. Desenko

Authors
  1. Mykola V. Protopopov
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  2. Olga V. Ostrynska
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  3. Sergiy A. Starosyla
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  4. Maria A. Vodolazhenko
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  6. Nikolay Yu. Gorobets
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  7. Volodymyr Bdzhola
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  9. Sergiy M. Yarmoluk
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Correspondence to Sergiy M. Yarmoluk.

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Protopopov, M.V., Ostrynska, O.V., Starosyla, S.A. et al. Dihydrobenzo[4,5]imidazo[1,2-a]pyrimidine-4-ones as a new class of CK2 inhibitors. Mol Divers 22, 991–998 (2018). https://doi.org/10.1007/s11030-018-9836-1

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  • DOI: https://doi.org/10.1007/s11030-018-9836-1

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