Efficient Oxidation of Cysteine and Glutathione Catalyzed by a Dinuclear Areneruthenium Trithiolato Anticancer Complex

Abstract

ABSTRACT:The highly cytotoxic diruthenium complex [(p-MeC 6 H 4 Pr i ) 2 Ru 2 (SC 6 H 4 -p-Me) 3 ] + (1), water-soluble as the chloride salt, is shown to efficiently catalyze oxidation of the thiols cysteine and glutathione to give the corresponding disulfides, which may explain its high in vitro anticancer activity.

Arene ruthenium complexes with phosphinoferrocene amino acid conjugates: Synthesis, characterization and cytotoxicity

“…Most compounds show only moderate cytotoxicities, only 7, 12c and 13c approach that of cisplatin in the A2789 cell line (IC 50 1.6 mM for A2780 and 8.6 mM for A2780 [15]). There is no clear-cut correlation between redox potentials and cytotoxicities, suggesting that catalytic glutathione oxidation, assumed for some other cytotoxic arene ruthenium complexes [24e26], in particular for dinuclear trithiolato derivatives [25,26] is not involved.…”

Challenges and Opportunities in the Development of Organometallic Anticancer Drugs

“…124 Interestingly, dimeric ruthenium(II)−arene trithiolato complexes have been shown to exert their antiproliferative behavior through catalytic processesan area of much potential interest to organometallic chemists. 125 In addition, numerous macroscopic polynuclear platinumcontaining systems, based on polymers, dendrimers, nanotubes, proteins, etc., have been developed in order to target cisplatin to tumors, spare healthy tissue, and reduce side effects. 126 Passive targeting of macromolecules to the tumor environment is possible due to their enhanced vascular permeability that is not present in the healthy endothelial layer surrounding the blood vessels feeding healthy tissue.…”

[(p-MeC6H4Pr )2Ru2(SC6H4-p-Bu )3]Cl (diruthenium-1), a dinuclear arene ruthenium compound with very high anticancer activity: An in vitro and in vivo study

“…Such a mitochondrial dysfunction typically augments the formation of reactive oxygen species (ROS) [38]. This is why we expected an increased oxidation of GSH, in addition to the previously demonstrated catalytic GSH oxidation under cell-free conditions [24,26]. During the incubation of cells with diruthenium-1, the intracellular levels of GSH actually decreased.…”

“…We observed interactions only with peptides and amino acids containing thiol functions. It turned out that this complex and its analogues are highly efficient catalysts for the oxidation of glutathione [26].…”