While medicinal inorganic chemistry has been practised for over 5000 years, it was not until the late 1800s when Alfred Werner published his ground-breaking research on coordination chemistry that we began to truly understand the nature of the coordination bond and the structures and stereochemistries of metal complexes. We can now readily manipulate and fine-tune their properties. This had led to a multitude of complexes with wide-ranging biomedical applications. This review will focus on the use and potential of metal complexes as important therapeutic agents for the treatment of cancer. With major advances in technologies and a deeper understanding of the human genome, we are now in a strong position to more fully understand carcinogenesis at a molecular level. We can now also rationally design and develop drug molecules that can either selectively enhance or disrupt key biological processes and, in doing so, optimize their therapeutic potential. This has heralded a new era in drug design in which we are moving from a single- toward a multitargeted approach. This approach lies at the very heart of medicinal inorganic chemistry. In this review, we have endeavored to showcase how a “multitargeted” approach to drug design has led to new families of metallodrugs which may not only reduce systemic toxicities associated with modern day chemotherapeutics but also address resistance issues that are plaguing many chemotherapeutic regimens. We have focused our attention on metallodrugs incorporating platinum and ruthenium ions given that complexes containing these metal ions are already in clinical use or have advanced to clinical trials as anticancer agents. The “multitargeted” complexes described herein not only target DNA but also contain either vectors to enable them to target cancer cells selectively and/or moieties that target enzymes, peptides, and intracellular proteins. Multitargeted complexes which have been designed to target the mitochondria or complexes inspired by natural product activity are also described. A summary of advances in this field over the past decade or so will be provided.

The concept of the “magic bullet”, a medicine designed to hit a specific biological target, was pioneered by Paul Ehrlich, the father of chemotherapy, some 100 years ago. Building on Ehrlich's vision, we have endeavoured to showcase not only how targeted PtIV prodrugs may be exploited to reduce systemic toxicities associated with modern‐day chemotherapeutics, including classical PtII drugs, but also how these prodrugs may overcome resistance issues that have plagued many chemotherapeutic regimes. A summary of advances in this field over the past decade is provided, with an emphasis on PtIV prodrugs that target not only DNA but also enzymes, proteins, peptides and hormones. Synthetic strategies for accessing PtIV chemistry are also provided.

In this chapter, we have endeavoured to showcase how some clinically approved drugs may be exploited as potential ligands when designing new metallodrugs to treat cancer. Interestingly, while there is a sound rationale behind repurposing existing drugs, those to date that have been tethered to platinum(ii) and platinum(iv) centres have not been chosen for this purpose. Rather, they have been selected because these drugs, in their own right, have exhibited potent anticancer activities albeit some are in clinical use for other indications. This chapter will provide an overview of some interesting platinum(ii) and platinum(iv) complexes incorporating a selection of clinically approved drugs or derivatives thereof as ligands. These complexes may form the basis of a new drug class which may offer advantages over existing therapeutic regimens.

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1 The prevalence and circumstance of digoxin prescribing was assessed in five private nursing homes. 2 Forty-one patients (21% residents) were taking digoxin. 3 Seventeen patients were in atrial fibrillation and the remainder in sinus rhythm. The ventricular rate exceeded 100 beats min-' in eight of the 17 patients in atrial fibrillation.4 Thirty-seven patients were prescribed 0.0625 mg digoxin daily and serum digoxin concentrations were subtherapeutic in 20 of 32 patients in whom concentrations were measured. 5 These data indicate a need for more careful review of the need for maintenance digoxin and illustrate the inappropriateness of routinely prescribing very low doses in all elderly patients.