Fiche publication
Date publication
avril 2025
Journal
Dalton transactions (Cambridge, England : 2003)
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GAIDDON Christian
,
Dr MELLITZER Georg
Tous les auteurs :
Scarpi-Luttenauer M, Galentino K, Orvain C, Fluck A, Cecchini M, Mellitzer G, Gaiddon C, Mobian P
Lien Pubmed
Résumé
To mimic the structural aspects of staurosporine, a potent but unspecific kinase inhibitor, several coordination compounds based on two readily available diimine ligands containing hydrogen bonding donor/acceptor sites (NH-CO fragment) have been designed and synthesized. These complexes are constructed around Ru(II) and Pt(II) metal centers. A total of 9 compounds, named Ru(1)-(5) and Pt(1)-(4), were obtained through straightforward synthetic approaches. The cytotoxicity of the compounds was evaluated on AGS gastric cancer cells (GC) through standard MTT assays. All ruthenium and platinum complexes with low toxicity, Ru(3), Ru(5), Pt(3) and Pt(4), were docked in the ATP binding pocket of two protein kinases (S6K1 and MST2). The docking scores highlighted a preferred affinity of Ru(5) for the MST2 binding pocket, whereas the platinum compounds are predicted to bind stronger to the S6K1 binding site. Inhibitory activity of the metal complexes on the MST2 and S6K1 signaling pathways was evaluated by analyzing western blot experiments the phosphorylation state of YAP, a downstream component of the Hippo pathway and the protein expression of S6 and its phosphorylated analogue p-S6. A clear difference of behavior between the Pt(II) and the Ru(II) complexes depending on the type of kinase was observed.
Référence
Dalton Trans. 2025 04 17;:
