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The search for anticancer metal-based drugs alternative to platinum derivatives could not exclude zinc derivatives due to the importance of this metal for the correct functioning of the human body. Zinc, the second most abundant trace element in the human body, is one of the most important micro-elements essential for human physiology. Its ubiquity in thousands of proteins and enzymes is related to its chemical features, in particular its lack of redox activity and its ability to support different coordination geometries and to promote fast ligands exchange. Analogously to other trace elements, the impairment of its homeostasis can lead to various diseases and in some cases can be also related to cancer development. However, in addition to its physiological role, zinc can have beneficial therapeutic and preventive effects on infectious diseases and, compared to other metal-based drugs, Zn(II) complexes generally exert lower toxicity and offer few side effects. Zinc derivatives have been proposed as antitumor agents and, among the great number of zinc coordination complexes which have been described so far, this review focuses on the design, synthesis and biological studies of zinc complexes comprising N-donor ligands and that have been reported within the last five years.

Zinc, present in all forms of life, is an essential element for humans. It is one of the most abundant metals in our body. Because of its importance, any malfunctions of its homeostasis can lead to different disease states, also related to the development of cancer. On the other hand, several Zn complexes have been recognized for their biological activities principally for preventive effects on infectious diseases and for low toxicity. Among different applications in medicinal chemistry, zinc-based complexes have shown to be appealing as anticancer drugs with low toxicity or as photosensitizers in photodynamic therapy. Here we present an overview of Zn coordination complexes proposed in the last six years as anticancer agents, trying to find a correlation between their chemical features and biological activity, and to evidence the potential perspectives of their use. Despite the great amount of work done in this field, this is the first exhaustive review on antitumor zinc complexes, that might be of wide interest for the researchers in the design and synthesis of new antitumor zinc-based drugs alternative to platinum derivatives.

In this framework AuNPs and AuNRs were synthetized with the aim to obtain strongly hydrophilic materials, suitable for drug delivery.[4-6] AuNPs were used as drug delivery systems for two different copper(I)-based anti-tumor complexes namely [Cu(PTA)4]+[BF4]- (A; PTA = 1,3,5-triaza-7-phosphadamantane) and [HB(pz)3Cu(PCN)] (B; HB(pz)3 = tris(pyrazolyl)borate, PCN = tris(cyanoethyl)phosphane).

Recently we have focused the research work on 11th group metal-NHCs complexes obtained from water soluble 1,3-symmetrically and 1,3-unsymmetrically substituted NHCs precursors based on imidazole and benzoimidazole scaffolds4-6...

Potentially bi-, tri- and tetra-dentate polyamines (1,3-diaminopropane (pn); diethylenetriamine (tren), tris(2-aminoethyl)amine (tetraen)) react with divalent zinc and copper nitrate salts in the presence of the 1,1-dicyano-2,2-ethylenedithiolate dipotassium salt (K2-mnt) to afford a variety of compounds in which the dithiolate acts as counter dianion or participates directly in metal coordination...

In this framework we report a study about drug delivery systems based on functi onalized AuNPs or AuNRs.

In this context, some investigations were performed to establish unequivocally the presence of caffeine/catechin complexes in green tea extracts (GTEs)......

Here we present the investigation on the [Cu(DAPTA)4][BF4]complex, where DAPTA = 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1] nonanefrom millimolar concentration down to 66 ?M, thus reaching concentration levels that can be correlated with those relevant for biological applications. Acquisition of XAS data on such a dilution level is very challenging and unusual. ...

In the present work the in vitroeffect of two metal complexes based on silver (Ag1 and Ag2) against the promastigote and amastigote forms of Leishmania amazonensisand L. guyanensiswere studied in 24, 48 and 72 hours.

Rationale [Cu(P)4][BF4]-type complexes (P = tertiary phosphine) have shown significant antitumor activity. This biological property appears to be activated via formation of coordinative unsaturated [Cu(P)n]+ species (n < 4), that may interact with various molecules starting from the solvent(s) in which they are dissolved. Aim of our study was to investigate the interaction of these species with different solvent mixtures. Methods The interaction has been investigated in electrospray ionization mass spectrometry, and the interaction products have been characterized by multiple collisional experiments, using an ion trap mass instrument. Density Functional Theory (DFT) calculations studies, using a meta-hybrid exchange correlation (xc) functional and an implicit solvent model, were employed to investigate the equilibrium distribution of species in solution. Results Depending on the nature of the solvent mixture and coordinated phosphine, three [Cu(P)4][BF4]-type complexes undergo dissociation with formation of [Cu(P)2]+, [Cu(P)(solv)]+ and [Cu(solv)2]+ species (solv = solvent). Preferred collisionally induced fragmentations pathways provide qualitative information on the selectivity of [Cu(P)n]+ for specific solvents and donor atoms. Formation free energies and equilibrium constants pertaining [CuI(PTA)n]+, [CuI/II(solv)n]m+ (n

Cisplatin is the archetypal inorganic drug and it is nowadays one of the most efficient metal-based anticancer agents, targeting a large number of solid tumours. Although highly effective in treating a variety of cancers, cisplatin treatment is still limited by severe side effects such as neuro-, hepato- and nephro-toxicity and by inherited or acquired resistance phenomena, only partially overcome by the use of new platinum drugs (i.e. oxaliplatin and carboplatin). These problems have stimulated the research and development of alternative therapeutic strategies based on different heavy metals. In this work we investigated the neurotoxicity effect of two new promising water soluble anticancer complexes based on copper [Cu(PTA)4PF6] and gold [Au(PTA)4PF6]. Cisplatin and oxaliplatin neurotoxicity was also measured as reference drugs. Neurotoxicity was evaluated by an in vitro model based on the ability of NGF exposed embryonic rat dorsal root ganglia (DRG) organotypic culture to grow neurite. In particular the interference of the under study neurotoxic compound with neurite elongation was analysed. DRGs explanted from E15 rat embryos were treated for 48h with different drug concentrations including the IC50 evaluated for different tumour cell lines. In our model cisplatin and oxaliplatin resulted neurotoxic (inducing a reduction of neurite outgrowth more than 50%) at concentrations achievable in plasma of patients treated with the same drugs confirming data obtained in clinical studies. On the contrary, the neurotoxicity assay demonstrated that copper-based compound was neurotoxic at higher concentrations with respect to the IC50 obtained for all tumour cell lines tested. On the other hand preliminary neurotoxicity data suggest that gold-based compound is neurotoxic at lower concentration than IC50 calculated for almost tested cancer cell lines. Our results, together with the low IC50 of the copper compound compared to the one observed for cisplatin and oxaliplatin, suggest that copper-based drugs represent new and promising compounds in anticancer treatment.

In this field novel1,3-symmetrically and 1,3-unsymmetrically substitutedNHCsprecursorshave been synthesized (Figure 1) and used in the synthesis of multicharged metal-NHC complexes...

RATIONALE To try to find a correlation between the antiproliferative activity of a series of [MI(P)4]+ complexes (M = Cu, Ag and Au; P = tertiary phosphine) and their stability at micromolar concentration under mass spectrometric conditions. METHODS [M I(P)4]+ complexes were investigated by positive ion electrospray ionization mass spectrometry with multiple collisional experiments using an ion trap mass spectrometer. RESULTS The displacement of P from native [MI(P)4]+, previously described for the copper derivative, is common for the triad complexes leading to the formation of [M(P)3]+ and [M(P)2]+ adducts. Further dissociation of [M(P)2]+ depends on the nature of the metal (Cu ~ Ag > Au). More labile [Cu(P)2] + and [Ag(P)2]+ are more cytotoxic against HCT-15 human colon carcinoma cells compared to less labile [Au(P) 2]+ species. CONCLUSIONS The dissociation of P ligand(s) from the [MI(P)4]+ complexes is the driving force for the triggering of the antiproliferative activity. The more favored is the displacement of P from the [M(P)2]+ active form, the more favored is in turn the possibility for the metal to interact with biological substrates related to cancer proliferation.