Glutathione Protects other Cellular Thiols against Oxidation by Cu-Dp44mT.

Cu-thiosemicarbazones have been intensively investigated for their application in cancer therapy or as antimicrobials. Copper(II)-di-2-pyridylketone-4,4-dimethyl-thiosemicarbazone (Cu-Dp44mT) showed anticancer activity in the submicromolar concentration range in cell culture. The interaction of Cu-Dp44mT with thiols leading to their depletion or inhibition was proposed to be involved in this activity.

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

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, which may be due to the generation of reactive oxygen species (ROS) by Dp44mT-bound Cu ions. However, in the intracellular environment, Cu complexes have to cope with glutathione (GSH), a relevant Cu reductant and Cu-chelator.