Classical and non-classical ruthenium-based anticancer drugs: Towards targeted chemotherapy

Ruthenium-based anticancer chemotherapies are making significant advances in clinical trials. Until recently, the focus has been on coordination complexes, and mechanisms such as activation by reduction and transferrin-targeted delivery have been proposed to account for the excellent cytotoxicity and low general toxicity of these complexes. More recently organoruthenium compounds, which to some extent appear not to follow the established rules, have started to be investigated. Despite such differences, similar activities between certain coordination and organometallic compounds suggest similar modes of action are present. DNA, the classic target, is believed to be the dominant mechanism for cytotoxicity with certain ruthenium drugs, while with others, non-classical targets are thought to be more important. In this article we describe these features and show how both ruthenium coordination complexes and organoruthenium compounds represent an ideal scaffold for further drug design and optimisation. ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006).