Medicinal inorganic chemistry can exploit the unique properties of metal ions for the design of new drugs. This has, for instance, led to the clinical application of chemotherapeutic agents for cancer treatment, such as cisplatin. The use of cisplatin is, however, severely limited by its toxic side-effects. This has spurred chemists to employ different strategies in the development of new metal-based anticancer agents with different mechanisms of action. Recent trends in the field are discussed in this review. These include the more selective delivery and/or activation of cisplatin-related prodrugs and the discovery of new non-covalent interactions with the classical target, DNA. The use of the metal as scaffold rather than reactive centre and the departure from the cisplatin paradigm of activity towards a more targeted, cancer cell-specific approach, a major trend, are discussed as well. All this, together with the observation that some of the new drugs are organometallic complexes, illustrates that exciting times lie ahead for those interested in 'metals in medicine'. DOI 10.1016DOI 10. /j.cbpa.2007 Introduction Medicinal inorganic chemistry [1 ,2,3] is a field of increasing prominence as metal-based compounds offer possibilities for the design of therapeutic agents not readily available to organic compounds. The wide range of coordination numbers and geometries, accessible redox states, thermodynamic and kinetic characteristics, and the intrinsic properties of the cationic metal ion and ligand itself offer the medicinal chemist a wide spectrum of reactivities that can be exploited. Although metals have long been used for medicinal purposes in a more or less empirical fashion [4], the potential of metal-based anticancer agents has only been fully realised and explored since the landmark discovery of the biological activity of cisplatin [5]. To date, this prototypical anticancer drug remains one of the most effective chemotherapeutic agents in clinical use. It is particularly active against testicular cancer and, if tumours are discovered early, an impressive cure rate of nearly 100% is achieved. The clinical use of cisplatin against this and other malignancies is, however, severely limited by dose-limiting side-effects such as neuro-, hepato-and nephrotoxicity [5]. In addition to the high systemic toxicity, inherent or acquired resistance is a second problem often associated with platinum-based drugs, which further limits their clinical use. Much effort has been devoted to the development of new platinum drugs and the elucidation of cellular responses to them to alleviate these limitations [5,6]. These problems have also prompted chemists to develop alternative strategies based on different metals and aimed at different targets. We summarize here recent activities in the field of metal-based anticancer drugs. This overview highlights some significant recent advances and illustrates emerging trends.
New modes of interaction with the classical target, DNAIn classical chemotherapy, anticancer agents target DNA ...
