The discovery of inhibitors of Fas-mediated cell death pathway using the combined computational method

Bioorg Med Chem Lett. 2013 Sep 15;23(18):5155-64. doi: 10.1016/j.bmcl.2013.07.018. Epub 2013 Jul 19.

Abstract

In this study, pharmacophore and 3D-QSAR models were developed for analogues of 3-substituted-benzofuran-2-carboxylate as inhibitors of Fas-mediated cell death pathways. Our pharmacophore model has good correspondence with experimental results and can explain the variance in biological activities coherently with respect to the structure of the data set compounds. The predictive power for our synthesized compounds were 0.96 for the pharmacophore model, 0.58 for the comparative molecular field analysis (CoMFA) model, and 0.57 for the comparative molecular similarity analysis (CoMSIA) model.

Keywords: 3D-QSAR; Fas-mediated cell death pathway; Pharmacophore.

MeSH terms

  • Benzofurans / chemical synthesis
  • Benzofurans / chemistry
  • Benzofurans / pharmacology*
  • Cell Death / drug effects
  • Drug Discovery*
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Quantitative Structure-Activity Relationship*
  • fas Receptor / antagonists & inhibitors*
  • fas Receptor / metabolism

Substances

  • Benzofurans
  • FAS protein, human
  • fas Receptor