Ruthenium Complexes that Mimic Platinum Drugs

The search for metal-based compounds able to bind irreversibly to DNA is generally considered as one of the most attractive directions of research exploited to develop anti-cancer drugs.7,10 12 Indeed, since its clinical introduction in the

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Figure 19.1 Cisplatin and its adduct with two guanine residues

Figure 19.1 Cisplatin and its adduct with two guanine residues late 1970s, cisplatin [cis-diamminedichloro-platinum(II)] remains one of the most efficient anti-cancer drugs. The cytotoxicity of this complex has been studied extensively and was shown to originate mainly from the formation of covalent cross-links that result from the binding of cisplatin to two purines of DNA (Figure 19.1).13,14 Such a substitution product (usually called adduct) is able to inhibit DNA and RNA synthesis and thereby induce cell death.15 Despite its important activity against various human cancers, cisplatin exhibits insufficient efficiency against some of the most frequent human cancers such as breast or colon tumors.16 Moreover, patients treated with cisplatin often undergo acquired resistance and heavy side effects.17

Both the advantages and the drawbacks of cisplatin chemotherapy have motivated scientists to search for other metal-based drugs with better therapeutic properties. Besides searching for platinum analogues, a further approach consists in developing anti-tumoral agents containing other metal ions such as ruthenium. In this section, we present different ruthenium complexes designed to mimic the action of platinum complexes and presenting either an in vitro or an in vivo anti-tumor activity. Thus, they belong to the first approach for the discovery of active compounds as described earlier.

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