180999-17-1Relevant academic research and scientific papers
Insights into the antiproliferative mechanism of (C^N)-chelated half-sandwich iridium complexes
Ramos, Robin,Zimbron, Jérémy M.,Thorimbert, Serge,Chamoreau, Lise-Marie,Munier, Annie,Botuha, Candice,Karaiskou, Anthi,Salmain, Michèle,Sobczak-Thépot, Jo?lle
, p. 17635 - 17641 (2020)
Transition metal-based anticancer compounds, as an alternative to platinum derivatives, are raising scientific interest as they may present distinct although poorly understood mechanisms of action. We used a structure-activity relationship-based methodology to investigate the chemical and biological features of a series of ten (C^N)-chelated half-sandwich iridiumIII complexes of the general formula [IrCp?(phox)Cl], where (phox) is a 2-phenyloxazoline ligand forming a 5-membered metallacycle. This series of compounds undergoes a fast exchange of their chlorido ligand once solubilised in DMSO. They were cytotoxic to HeLa cells with IC50 values in the micromolar range and induced a rapid activation of caspase-3, an apoptosis marker. In vitro, the oxidative power of all the complexes towards NADH was highlighted but only the complexes bearing substituents on the oxazoline ring were able to produce H2O2 at the micromolar range. However, we demonstrated using a powerful HyPer protein redox sensor-based flow cytometry assay that most complexes rapidly raised intracellular levels of H2O2. Hence, this study shows that oxidative stress can partly explain the cytotoxicity of these complexes on the HeLa cell line and gives a first entry to their mechanism of action. This journal is
Chiral β-amino sulfoxides. Synthesis, configurational assignment and conformational analysis based on X-ray, CD, 1H NMR and theoretical calculations
Lewanowicz,Lipinski,Siedlecka,Skarzewski,Baert
, p. 6571 - 6586 (2007/10/03)
Enantiomerically pure u and l β-amino sulfoxides have been easily obtained from the respective homochiral α-amino alcohols. The absolute configuration at the created stereogenic centre was assigned by CD spectra and by X-ray analysis. Conformational analysis of the title compounds was carried out using quantum chemical energy-geometry optimization. Thus established conformational behavior explained the strongly configuration dependent NMR spectral patterns observed for the u and l diastereomers.
