Abstract
Cancer is nowadays one of the leading causes of death in the developed world. Biologically, cancer represents a vastly heterogenic group of diseases sharing several common traits. One of these hallmarks is sustained proliferation, resulting in uncontrolled tumour growth (Hanahan and Weinberg, 2011 ). An extensive research has been done to characterize antiproliferative effect of various classes of compounds, ranging from naturally occurring molecules and their derivatives, to organometallic and inorganic compounds and their application in cancer therapy. The fortuitous discovery of the cytotoxic properties of cisplatin (diamminedichloroplatinum (II)) in 1965, opened new avenue for the application of metal complexes in cancer therapy (Arnesano et al., 2011) (Fig. 1 ). The antiproliferative effect of cisplatin and other compounds, however, induces adverse effects on normal tissues, decreasing therapeutic effectivity. Moreover, in many cancers, tumour cells may acquire resistance to the metal-based cytotoxic therapy resulting in virtually incurable relapsing disease (Desoize, 2004) . In the last 15 years, a great effort has been dedicated to the development of more effective and less toxic drugs. Various new trans-platinum(II) and platinum(IV) complexes have been synthesized, and some of them have been selected for clinical trials (Kelland et al., 1999) , but with varying effectivity and safety. Therefore, less toxic metals, such as ruthenium, gold or copper were introduced as promising candidates for effective and safe therapy (Tiekink, 2002; Clarke, 2002; Marzano et al., 2009; Nobili et al., 2010) . Various reviews have been published on the use of metal complexes as anticancer agents, with the intent to give an overview of the proposed approaches concerning the application of these systems in clinical practice (Tiekink, 2002; Boulikas et al., 2007; Milacic et al., 2008; Bruijnincx and Sadler, 2008; Todd and Lippard, 2009; Vilmar and Sørensen, 2009; Esteban-Fernández et al., 2010; Tisato et al., 2010; Wang and von Recum, 2011; Beija et al., 2012; Babu et al., 2013; Maldonado et al., 2013; Sukumar et al., 2013; Cao-Milán and Liz-Marzán, 2014; Mjos and Orvig, 2014; Muhammad and Guo, 2014; Petrelli et al., 2014) . However, the majority of the available reviews point out the most relevant examples of platinum-or non-platinumbased compounds, eventually focusing on one particular metal ion or making a compendium on two or more metal ions. The aim of this review is to bridge a gap by summarizing on historical background, novel trends in synthesis of new metal complexes with antiproliferative effects and to describe their chemical reactivity, pharmacokinetic properties and interactions in the biological and biomedical context.
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