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Medicinal Chemistry Research

, Volume 21, Issue 8, pp 1912–1920 | Cite as

Docking and quantitative structure–activity relationship studies for imidazo[1,2-a]pyrazines as inhibitors of checkpoint kinase-1

  • Julio CaballeroEmail author
  • Szymon Zilocchi
  • William Tiznado
  • Simona Collina
Original Research

Abstract

We have performed docking of imidazo[1,2-a]pyrazines complexed with checkpoint kinase1 (Chk1) to better understand the structural requirements and preferred conformations of these inhibitors. The study was performed on a selected set of 33 compounds with variation in structure and activity. In addition, the predicted inhibitor concentrations (IC50) of the imidazo[1,2-a]pyrazines as Chk1 inhibitors were obtained by comparative molecular similarity analysis (CoMSIA). The best CoMSIA model included electrostatic and hydrophobic fields, had a good Q 2 value of 0.589, and adequately predicted the compounds contained in the test set. Furthermore, plots of the CoMSIA fields allowed conclusions to be drawn for the selection of suitable inhibitors.

Keywords

Checkpoint kinase-1 inhibitors Molecular docking Quantitative structure–activity relationships CoMSIA 

Notes

Acknowledgements

Julio Caballero thanks “Becas Universidad de Talca” for financial support through doctoral fellowship. Part of this work has been supported by Fondecyt, Grant 11090431, Proyecto interno DI-13-10/R, Universidad Andres Bello.

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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Julio Caballero
    • 1
    Email author
  • Szymon Zilocchi
    • 2
    • 3
  • William Tiznado
    • 3
  • Simona Collina
    • 2
  1. 1.Centro de Bioinformática y Simulación Molecular, Facultad de Ingeniería en BioinformáticaUniversidad de TalcaCasilla 721, TalcaChile
  2. 2.Department of Pharmaceutical ChemistryUniversity of PaviaPaviaItaly
  3. 3.Departamento de Ciencias Químicas, Facultad de Ecología y Recursos NaturalesUniversidad Andres BelloSantiagoChile

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