Antitumour metal compounds: more than theme and variations

Abstract

Triggered by the resounding success of cisplatin, the past decades have seen tremendous efforts to produce clinically beneficial analogues. The recent achievement of oxaliplatin for the treatment of colon cancer should, however, not belie the imbalance between a plethora of investigated complexes and a very small number of clinically approved platinum drugs. Strategies opening up new avenues are increasingly being sought using complexes of metals other than platinum such as ruthenium or gallium. Based on the chemical differences between these metals, the spectrum of molecular mechanisms of action and potential indications can be broadened substantially. Other approaches focus on complexes with tumour-targeting properties, thereby maximizing the impact on cancer cells and minimizing the problem of adverse side effects, and complexes with biologically active ligands.

Comparative solution equilibrium studies of anticancer gallium(III) complexes of 8-hydroxyquinoline and hydroxy(thio)pyrone ligands

“…8. In both cases, the predominant complexes are the [GaL 3 ] species under the applied conditions and, as expected, the partial dissociation resulting in free ligand and [Ga(OH) 4 ] − is more pronounced with decreasing total concentrations.…”

“…Numerous gallium(III) complexes inhibit tumor growth and Ga was the second metal ion, after platinum to be administered to cancer patients in various clinical trials [1][2][3][4]. Ga is used in a wide variety of applications, such as medical imaging for some cancer types, infections and inflammatory diseases in form of 67 Ga(III) and 68 Ga(III) radiopharmaceuticals [5] and fluorescent Ga(III) compounds possibly in organic light-emitting diodes [6].…”

“…Orally administered Ga(III) salts are not sufficiently bioavailable. A prolonged exposure of low steady-state Ga(III) concentration in the blood can result in an improved therapeutic index, that can be assured by application of charge neutral Ga(III) complexes [4]. Accordingly, many compounds have been prepared and tested by in vitro and in vivo studies.…”

Interactions of arene ruthenium metallaprisms with human proteins

“…3,4 The increased selectivity represents the most important feature of the newly developed drugs in order to minimize side effects and to prevent the development of resistance mechanisms. 5,6 As emphasized in the literature, in order to successfully design and develop new and selective metal-based drugs, it is of the highest importance to understand the mode of action of established and also of newly developed anticancer drugs. 7,8 Among the new generation of metal-based drugs, ruthenium derivatives appear to be quite promising.…”

Conjugation of a Ru(II) Arene Complex to Neomycin or to Guanidinoneomycin Leads to Compounds with Differential Cytotoxicities and Accumulation between Cancer and Normal Cells

“…[6][7][8][9][10][11][12] In medicinal chemistry terms, their "piano-stool" structure allows the optimization of lead compounds through structureactivity relationship studies by modifying ligands around the metallic center. [15][16] Among such modifications, derivatization of non-leaving ligands with a carrier molecule has tremendous potential to generate selective, less toxic metallodrugs. The potential of this targeted strategy is particularly promising when metal complexes, either organometallic or classical coordination compounds, are attached to biomolecules [17][18][19][20][21][22][23][24] whose receptors are overexpressed on the membrane of tumoral cells [25][26][27][28] or to organic molecules with high affinity with a given biological target (proteins or nucleic acids).…”