Discovery of the metallopharmaceutical cisplatin and its use in antitumour therapy has initiated the rational design and screening of metal-based anticancer agents as potential chemotherapeutics. In addition to the achievements of cisplatin and its therapeutic analogues, there are significant drawbacks to its use: resistance and toxicity. Over the past four decades, numerous transition metal complexes have been synthesized and investigated in vitro and in vivo. The most studied metals among these complexes are platinum and ruthenium. The key features of these investigations is to find novel metal complexes that could potentially exert less toxicity and equal or higher antitumour potency and to overcome other pharmacological deficiencies. Ru complexes have a different mode of action than cisplatin does, some of which are under clinical trials for treating metastatic or cisplatin-resistant tumours. This review consists of the current knowledge, published and unpublished, related to the toxicity of metallopharmaceuticals, and special attention is given to platinum [Pt(II) and Pt(IV)] and ruthenium [Ru(II) and Ru(III)] complexes.
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