Ruthenium anticancer compounds

Bratsos I, Jedner S, Gianferrara T, Alessio E (2007) Ruthenium anticancer compounds challenges and expectations. Chimia 61 692-697... 

Fig. 13.2 Examples of clinically investigated ruthenium anticancer compounds...

Scheme 5.5 Selected titanium and ruthenium anticancer compounds.

Three ruthenium anticancer compounds a) imidazolium trans-tetrachlorobis(imidazole) ruthenate(III), Him trans-[RuCl4(im)2] (6) indazolium trans-tetrachlorobis(indazole) ruthenate(III), Hind trans-[RuCl4(ind)2] ... 

Nazarov, A. A. et al. Anthracene-Tethered Ruthenium(II) Arene Complexes as Tools To Visualize the Cellular Localization of Putative Organometallic Anticancer Compounds. Inorg. Chem. 51, 3633-3639 (2012). 

Hanif, M., Nazarov, A. A., Hartinger, C. G., Kandioller, W., Jakupec, M. A., Arion, V. B., Dyson, P. J. Keppler, B. K. Osmium(ii)-versus ruthenium(ii)-arene carbohydrate-based anticancer compounds similarities and differences. Dalton... 

Anticancer compounds (continued) ruthenium arene compounds, 12, 451 selective estrogen receptor modulators, 12, 446 titanocenes, 12, 450... 

Therrien et al. have developed organometallic ruthenium porphyrin compounds for anticancer photodynamic therapy. These combine synergistically the photodynamic action of porphyrins with the DNA damage-related cytotoxicity of Run-arene... 

Mendoza-Ferri M-G, Hartinger CG, Eichinger RE, Stolyarova N, Severin K, Jakupec MA, Nazarov AA, Keppler BK (2008) Influence of the spacer length on the in vitro anticancer activity of dinuclear ruthenium-arene compounds. Organometallics 27 2405-2407... 

Dale LD, Tocher JH, Dyson TM, Edwards DI, Tocher DA (1992) Studies on DNA damage and induction of SOS repair by novel multifunctional bioreducible compounds. II. A metronidazole adduct of a ruthenium-arene compound. AntiCancer Drug Des 7 3-14... 

Ang WH, Daldini E, Juillerat-Jeanneret L, Dyson PJ (2007) Strategy to tether organometallic ruthenium-arene anticancer compounds to recombinant human serum albumin. Inorg Chem 46(22) 9048-9050... 

Piccioli F, Sabatini S, Messori L, Orioli P, Hartinger CG, Keppler BK (2004) A comparative study of adduct formation between the anticancer ruthenium(III) compound Hind trans-[RuCl4(Ind)2] and serum proteins. J Inorg Biochem 98 1135-1142... 

Bratsos, T. Gianferrara, E, Alessio, C. G. Hartinger, M. A. Jakupec, and B. K. Keppler. (2011). Chapter 5 Ruthenium and other non-platinum anticancer compounds. In Alessio, E. (ed,). Bioinorganic Medicinal Chemistry. Weinheim Wiley-VCH Verlag Co. 

Figure 3 A selection of anticancer-active Ruthenium coordination compounds. The compounds NAM FA (1) and NAMl (2), each have an imidazolium as a counter cation a very active compound (3) of the a isomer of a Ru-azpy compound (azpy = 2-phenylazopyridine) and a Ru-terpy compound (4). From these NAMFA has been in clinical trials since 2000.

Hanif M, Nazarov AA, Hartinger CG et al (2010) Osmium(II)- veisus ruthenium(II)-arene carbohydratebased anticancer compounds similarities and differences. Dalton Trans 39 ... 

The first report on the anticancer properties of ruthenium was published in 1976 when the Ru(III) compound /ac-[RuC13(NH3)3] (Fig. 11) was found to induce filamentous growth of Escherichia coli at concentrations comparable to those at which cisplatin generates similar effects (49). This Ru(III) complex and related compounds such as cis-[RuCl2(NH3)4]Cl illustrated the potential anticancer activity of ruthenium complexes, but insolubility prevented further pharmacological use. Since these initial studies, other Ru(III) complexes have been studied for potential anticancer activity, and two compounds, NAMI-A (50) and KP1019 (51), are currently undergoing clinical trials. Remarkably,... 

Fig. 11. Molecular structures of (a) fac-[RuCl3(NH3)3], the first reported ruthenium complex with anticancer activity, and (b) NAMI-A and KP1019, two ruthenium compounds currently in clinical trials.

It is well established that the major cytotoxic effect of platinum-based anticancer dmgs stems from binding of the platinum centre to DNA. The coordination of platinum(II) centres to DNA causes structural modifications which ultimately lead to the induction of apoptosis. Ruthenium compounds were developed as alternatives to platinum compounds and initially their binding to DNA, similarly to platinum compounds, was considered to be central for their anticancer effect. The ruthenium... 

As far as we are aware the first example of a ruthenium(II)-arene compound to be evaluated for anticancer activity was described by Tocher and co-workers in 1992 [18]. The field remained essentially dormant until the explosion in interest led largely by our group and that of Sadler, who has extensively studied ruthenium(II)-arene complexes with ethylenediamine and related ligands, and describes these compounds in the Chapter X in this book. It should be noted that other groups have also contributed to the field as will become clear in the course of this Chapter. 

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