Ruthenium anticancer drug complexes

Alessio E, Mestroni G, Bergamo A, Sava G (2004) Ruthenium anticancer drugs. In Sigel H (ed) Metal Complexes in Tumor Diagnosis and as Anticancer Agents. CRC Press, USA, pp 323-351... 

Fig. 2. Ligand substitution as a prodrug strategy for metallochem-otherapeutics (a) general scheme of prodrug activation by ligand substitution hydrolysis of a metal—halide bond is a typical activation pathway of metal-based anticancer drugs, as exemplified by the activation of cisplatin (b) and a ruthenium—arene complex (c).

This work provides important evidence for elucidating the cytotoxic effect of the ruthenium-arene complexes and the influence of the arene thereon, for instance with respect to excision repair of DNA lesions and DNA destabilization. It also established two different classes of Ru(II) arene anticancer drugs, i.e. those bearing an arene that has the possibility to intercalate and those that do not. This distinction is important as we will see further differences in DNA binding interactions for these two classes (vide infra). 

Because of the severe side effects, the restricted tumour spectrum and the acquired or intrinsic resistance, alternative metal-based anticancer drugs are being actively pursued. Ruthenium compounds containing Ru or Ru are considered to be suitable candidates two mthenium(III) complexes have entered clinical trials, trans-[RuCl4(DMSO)(Im)]ImH (NAMI-A, where Im = imidazole) and trans-[RuCl4(Ind)2]IndH (KP1019, where Ind = indazole). This is the mthenium complex, their stmctures are presented in Figure 22.9. There are two... 

The metal ruthenium possesses several favorable chemical properties and it may be a strong candidate to form a basis for rational anticancer drug design [104,105]. For instance, several ruthenium(II) and ruthenium(III) complexes (Scheme 5.5) exhibit a high antitumor activity both in vitro and in vivo [2,106,107]. Therefore, the reactions of Ru and Ru complexes with DNA and sulfur-containing amino acids as well as proteins has been studied by NMR and other spectroscopic methods (e.g. HPLC). Such studies may facilitate the development of an additional structure-activity relationship and allow more selective, potent and less toxic anticancer drugs to be designed. 

Ruthenium(II) complexes of the general type shown below are potential anticancer drugs ... 

Theory, experiment and reaction rates a personal view . J. Reedijk (2008) Platinum Metals Rev., vol. 52, p. 2 - Metal-ligand exchange kinetics in platinum and ruthenium complexes. Significance for effectiveness as anticancer drugs . 

Figure 15.11 Heterobimetallic NHC-Au /Ru" complexes envisioned as anticancer drugs that could be imaged by utilizing the luminescence of the ruthenium(ii) moiety.

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