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.

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.