Dual Role of Glutathione as a Reducing Agent and Cu-Ligand Governs the ROS Production by Anticancer Cu-Thiosemicarbazone Complexes.
Inorg Chem
; 62(9): 3957-3964, 2023 Mar 06.
Article
em En
| MEDLINE
| ID: mdl-36802558
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 CuII, which may be due to the generation of reactive oxygen species (ROS) by Dp44mT-bound CuII ions. However, in the intracellular environment, CuII complexes have to cope with glutathione (GSH), a relevant CuII reductant and CuI-chelator. Here, aiming at rationalizing the different biological activity of Triapine and Dp44mT, we first evaluated the ROS production by their CuII-complexes in the presence of GSH, showing that CuII-Dp44mT is a better catalyst than CuII-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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tiossemicarbazonas
/
Antineoplásicos
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article