Identification of Eukaryotic Translation Elongation Factor 1-α 1 Gamendazole-Binding Site for Binding of 3-Hydroxy-4(1 H)-quinolinones as Novel Ligands with Anticancer Activity

J Med Chem. 2018 Apr 12;61(7):3027-3036. doi: 10.1021/acs.jmedchem.8b00078. Epub 2018 Mar 16.


Here, we have identified the interaction site of the contraceptive drug gamendazole using computational modeling. The drug was previously described as a ligand for eukaryotic translation elongation factor 1-α 1 (eEF1A1) and found to be a potential target site for derivatives of 2-phenyl-3-hydroxy-4(1 H)-quinolinones (3-HQs), which exhibit anticancer activity. The interaction of this class of derivatives of 3-HQs with eEF1A1 inside cancer cells was confirmed via pull-down assay. We designed and synthesized a new family of 3-HQs and subsequently applied isothermal titration calorimetry to show that these compounds strongly bind to eEF1A1. Further, we found that some of these derivatives possess significant in vitro anticancer activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology*
  • Binding Sites / drug effects
  • Cell Line, Tumor
  • Computational Biology
  • Humans
  • Indazoles / metabolism*
  • Ligands
  • Models, Molecular
  • Molecular Conformation
  • Peptide Elongation Factor 1 / biosynthesis
  • Peptide Elongation Factor 1 / drug effects*
  • Quinolones / chemical synthesis*
  • Quinolones / pharmacology*
  • Structure-Activity Relationship


  • Antineoplastic Agents
  • EEF1A1 protein, human
  • Indazoles
  • Ligands
  • Peptide Elongation Factor 1
  • Quinolones
  • gamendazole