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Journal of Computer-Aided Molecular Design

, Volume 27, Issue 8, pp 739–754 | Cite as

Human farnesyl pyrophosphate synthase inhibition by nitrogen bisphosphonates: a 3D-QSAR study

  • David Fernández
  • Joaquín Ortega-Castro
  • Juan Frau
Article

Abstract

We report the results of a comparative molecular field analysis and comparative molecular similarity index analysis of the human farnesyl pyrophosphate synthase (FPPS) inhibition by nitrogen bisphosphonates (NBPs) taking into account their time-dependent inhibition efficacies. The 3D-QSAR models obtained provide steric, electrostatic and hydrophobic contour maps consistent with the interactions into the active site of human FPPS observed in available crystallographic structures. Furthermore, the 3D-QSAR models obtained provide accurately IC50 values of the NBPs of the training set. The predictive ability of these 3D-QSAR models was found to rely on the choice of biologically active conformations of the target molecules and on a careful examination of the protonation status of the NBPs in the training set. The best models obtained can be useful to predict biological values of a high number of NBPs that have been used for the treatment of different diseases as potential inhibitors of the activity of the FPPS enzyme.

Keywords

Bisphosphonates 3D-QSAR Human farnesyl pyrophosphate synthase Inhibitors 

Supplementary material

10822_2013_9674_MOESM1_ESM.doc (1.9 mb)
Supplementary material 1 (DOC 1918 kb)

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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • David Fernández
    • 1
  • Joaquín Ortega-Castro
    • 1
  • Juan Frau
    • 1
  1. 1.Departament de Química, Institut Universitari d’Investigació en Ciències de la Salut (IUNICS)Universitat de les Illes BalearsPalma de MallorcaSpain

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