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
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Quinolones chemical synthesis pharmacology MeSH
- Peptide Elongation Factor 1 biosynthesis drug effects MeSH
- Indazoles metabolism MeSH
- Humans MeSH
- Ligands MeSH
- Molecular Conformation MeSH
- Models, Molecular MeSH
- Cell Line, Tumor MeSH
- Antineoplastic Agents chemical synthesis pharmacology MeSH
- Binding Sites drug effects MeSH
- Computational Biology MeSH
- Structure-Activity Relationship MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Quinolones MeSH
- EEF1A1 protein, human MeSH Browser
- Peptide Elongation Factor 1 MeSH
- gamendazole MeSH Browser
- Indazoles MeSH
- Ligands MeSH
- Antineoplastic Agents MeSH
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.
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