Exploring diversity in platinum(iv) N-heterocyclic carbene complexes: synthesis, characterization, reactivity and biological evaluation.
Fiche publication
Date publication
août 2018
Journal
Dalton transactions (Cambridge, England : 2003)
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BELLEMIN-LAPONNAZ Stéphane
Tous les auteurs :
Bouché M, Bonnefont A, Achard T, Bellemin-Laponnaz S
Lien Pubmed
Résumé
Platinum(iv) complexes stabilized by N-heterocyclic carbene ligands of the type [(NHC)PtX4L], where L is a neutral nitrogen-based ligand and X is a halide anion (Br, Cl), were prepared by using straightforward and high-yielding synthetic routes and the scope was extended to amphiphilic derivatives. The complexes were fully characterized and the molecular structure of the three derivatives was determined by single-crystal X-ray analyses. The complexes demonstrated in vitro antiproliferative activities against several cancer cell lines. In particular, a representative Pt(iv) complex, namely, [(NHC)PtCl4(pyridine)], displayed efficient antiproliferative activity against cisplatin-resistant cancer cells. These results were correlated with their physicochemical properties, namely, solubility, stability and redox behavior by means of UV-vis spectroscopy, NMR or cyclic voltammetry, whereas in DMSO/water, these Pt(iv) complexes transform into biologically less active cis[(NHC)PtX2(DMSO)] species, in the presence of a bioreductant such as glutathione which quickly leads to the formation of a biologically active trans[(NHC)PtX2L] complex. Overall, these data show that NHC-Pt(iv) compounds are good candidates as anti-cancer prodrugs.
Mots clés
Antineoplastic Agents, chemical synthesis, Cell Line, Tumor, Chemistry Techniques, Synthetic, Dimethyl Sulfoxide, chemistry, Drug Resistance, Neoplasm, drug effects, Drug Stability, Glutathione, metabolism, Heterocyclic Compounds, chemistry, Humans, Methane, analogs & derivatives, Models, Molecular, Molecular Conformation, Organoplatinum Compounds, chemical synthesis, Oxidation-Reduction, Water, chemistry
Référence
Dalton Trans. 2018 Aug 3;: