Inorganic Chemistry [BCB/POMAN]

Abstract

α-Pyridyl thiosemicarbazones (TSC) such as Triapine (3AP) and Dp44mT are a promising class of anticancer agents. Contrary to Triapine, Dp44mT showed a pronounced synergism with Cu^II, which may be due to the generation of reactive oxygen species (ROS) by Dp44mT-bound Cu^II ions. However, in the intracellular environment, Cu^II complexes have to cope with glutathione (GSH), a relevant Cu^II reductant and Cu^I-chelator. Here, aiming at rationalizing the different biological activity of Triapine and Dp44mT, we first evaluated the ROS production by their Cu^II-complexes in the presence of GSH, showing that Cu^II-Dp44mT is a better catalyst than Cu^II-3AP. Furthermore, we performed density functional theory (DFT) calculations, which suggest that a different hard/soft character of the complexes could account for their different reactivity with GSH.

 

Reference

Dual Role of Glutathione as a Reducing Agent and Cu-Ligand Governs the ROS Production by Anticancer Cu-Thiosemicarbazone Complexes

Alessandra G Ritacca, Enrico Falcone, Iman Doumi, Bertrand Vileno, Peter Faller, and Emilia Sicilia

Inorganic Chemistry, Publication date February 20 – DOI:  10.1021/acs.inorgchem.2c04392

Contact

Peter Faller (team BCB), Institut de Chimie de Strasbourg (UMR 7177).