An overview of advancement of organoruthenium(II) complexes as prospective anticancer agents

Abstract

The successful clinical translation of platinum drugs for cancer treatment has witnessed an upsurge in the development of metal compounds as therapeutics and diagnostics drugs. However, owing to severe toxicity and multifaceted drug resistance associated with platinum drugs, non-platinum anticancer agents especially featuring ruthenium have emerged as the most promising alternatives. The lower general toxicity exhibited by ruthenium complexes has been attributed to their ability of specific accumulation and a consequent activation by reduction mechanism within the tumour cell environment. In recent years, special emphasis has been given to organoruthenium(II) complexes on account of their favourable biochemical properties which include high lipophilic character, kinetic stability and specific mode of therapeutic action. Moreover, the use of structure activity relationship (SAR) and the state-of-the art targeted chemotherapy has allowed significant dominance of cytotoxic organoruthenium(II) compounds in the chemotherapeutic drug regime. In the present review, we have provided an overview of the latest advancements in developing organoruthenium(II) compounds as prospective anticancer agents and as alternatives to platinum drugs. It commences by identifying the different mechanism of anticancer action and signalling pathways that lend organoruthenium(II) complexes remarkable cytotoxic potential. Next, the review specifically highlights the cytotoxic assessment of various classes of organoruthenium(II) complexes based on diverse ligand frameworks that hold promise as potential anticancer drug candidates. We have further highlighted the progress of some archetypal ruthenium-arene complexes which are presently in pre-/clinical trials or have potential to be translated in clinical practice.