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

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) ca

SUBMITTER: Ritacca AG 

PROVIDER: S-EPMC9996813 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature