Reduction and Subsequent Binding of Ruthenium Ions Catalyzed by Subcellular Components

Anticancer activity of multinuclear arene ruthenium complexes coordinated to dendritic polypyridyl scaffolds

“…The majority of ruthenium compounds evaluated for anticancer activity are coordination compounds with the ruthenium in the +3 oxidation state. It has been proposed that in this oxidation state ruthenium is less active and is reduced in vivo to more active ruthenium(II) complexes, a process favoured in the hypoxic environment of a tumour [11]. However, it should be noted that ruthenium(II) compounds also exhibit a low general toxicity and since cancer cells can also become oxidized at certain stages of their growth cycle oxidation of the ruthenium cannot be excluded [12].…”

Phase I/II study with ruthenium compound NAMI-A and gemcitabine in patients with non-small cell lung cancer after first line therapy

“…[17] In tumor tissue, due to the more reducing environment, re-oxidation of Ru(II) to Ru(III) is less likely to occur, thus leading to an accumulation of active species. [13,17] This would not only imply selective efficacy, but also selective toxicity [12,13,18]. 3) Slow ligand exchange kinetics: most administered metal drugs undergo spontaneous modifications prior to reaching the target (typically, some ligands are released) and therefore ligand exchange kinetics in ruthenium compounds is an important factor.…”

Using coordination chemistry to design new medicines

“…Whilst KP1019 is cytotoxic to cancer cells, NAMI-A is relatively non-toxic but has antimetastatic activity (prevents the spread of cancer). Clarke has proposed that the activity of Ru(III) complexes, which are usually relatively inert towards ligand substitution, is dependent on in vivo reduction to more labile Ru(II) complexes [67,70]. With this in mind, we have explored the activity of Ru(II) complexes.…”