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Medicinal Chemistry Research

, Volume 26, Issue 11, pp 2809–2815 | Cite as

Choline kinase inhibition and docking studies of a series of 6-(benzylthio)-9H-purin-9-yl-pyridinium derivatives

  • Belén Rubio-Ruiz
  • Pablo Ríos-Marco
  • María Paz Carrasco-Jiménez
  • Antonio Espinosa
  • Ramon Hurtado-Guerrero
  • Carmen Marco
  • Ana Conejo-García
  • Antonio Entrena
Original Research

Abstract

Human choline kinase is a well validated target for the treatment of cancer. In the last two decades, many choline kinase inhibitors have been developed and one of them is currently under evaluation in clinical trials. In this paper a series of 6-(benzylthio)-9H-purin-9-yl-pyridinium derivatives were evaluated as choline kinase inhibitors, and their effects on cell proliferation were also investigated in the human hepatoma HepG2 cell line. The most potent inhibitor against purified choline kinase-α1 presents an IC50 value of 0.4 μM. The biological data and the docking studies described here, support that the 4-(dimethylamino)pyridinium cationic head and a small linker (benzene or biphenyl) are the essential structural parameters for choline kinase inhibition of the tested compounds.

Keywords

Choline kinase Inhibitors Pyridinium compounds Antiproliferative agents Lipophilicity 

Notes

Acknowledgements

We thank the ‘Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía’ (Excellence Research Project no. P07-CTS-03210) and the ‘Ministerio de Ciencia e Innovación’ (Project no. SAF2009-11955) for the financial support. The award of grants from the ‘Ministerio de Educación’ to B.R.-R. and P.R.-M. is gratefully acknowledged.

Conflicts of Interest

The authors declare that they have no competing interests.

Supplementary material

44_2017_1979_MOESM1_ESM.docx (5.1 mb)
Supplementary Information

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Belén Rubio-Ruiz
    • 1
  • Pablo Ríos-Marco
    • 2
  • María Paz Carrasco-Jiménez
    • 2
  • Antonio Espinosa
    • 1
  • Ramon Hurtado-Guerrero
    • 3
  • Carmen Marco
    • 2
  • Ana Conejo-García
    • 1
  • Antonio Entrena
    • 1
  1. 1.Department of Pharmaceutical and Organic Chemistry Faculty of PharmacyUniversity of GranadaGranadaSpain
  2. 2.Department of Biochemistry and Molecular Biology I Faculty of SciencesUniversity of GranadaGranadaSpain
  3. 3.Institute for Biocomputation and Physics of Complex Systems (BIFI)University of ZaragozaZaragozaSpain

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