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.
- MeSH
- antitumorózní látky chemická syntéza farmakologie MeSH
- chinolony chemická syntéza farmakologie MeSH
- elongační faktor 1 biosyntéza účinky léků MeSH
- indazoly metabolismus MeSH
- lidé MeSH
- ligandy MeSH
- molekulární konformace MeSH
- molekulární modely MeSH
- nádorové buněčné linie MeSH
- vazebná místa účinky léků MeSH
- výpočetní biologie MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
