Zinc(II) complexes with dithiocarbamato derivatives: structural characterisation and biological assays on cancerous cell lines.

Zinc is one of the most important trace elements in the body and it is essential as a cofactor for the structure and function of a number of cellular molecules including enzymes, transcription factors, cellular signalling proteins and DNA repair enzymes. On the other hand, recent studies have shown that zinc could play a role both in the development of various cancers and in the induction of apoptosis in some cell types, however, no established common relationships of zinc with cancer development and progression have been identified. To date, in our research group different metal-dithiocarbamato complexes have been designed that were expected to resemble the main features of cisplatin together with higher activity, improved selectivity and bioavailability, and lower side-effects.

Rational design of gold(III)-dithiocarbamato peptidomimetics for the targeted anticancer chemotherapy.

As a further extension of our research work focusing on the development of gold(III)-dithiocarbamato dtc derivatives of oligopeptides as potential anticancer agents, complexes [Au(III)X(2)(dtc-Sar-L-Ser(t-Bu)-O(t-Bu))] (X=Br (1a)/Cl (1b)), [Au(III)X(2)(dtc-AA-Aib(2)-O(t-Bu))] (AA=Sar (sarcosine, N-methylglycine), X=Br (2a)/Cl (2b); AA=D,L-Pro, X=Br (3a)/Cl (3b)), [Au(III)X(2)(dtc-Sar-Aib(3)-O(t-Bu))] (X=Br (4a)/Cl (4b)), and [Au(III)X(2)(dtc-Sar-Aib(3)-Gly-OEt)] (X=Br (5a)/Cl (5b)) (Aib = "alpha"-aminoisobutyric acid, 2-methylalanine) were designed to obtain metal-based peptidomimetics that may specifically target two peptide transporters (namely, PEPT1 and PEPT2) upregulated in several human tumor cells. All the compounds were characterized by means of FT-IR and mono- and multidimensional NMR spectroscopy. According to in vitro cytotoxicity studies, complex [Au(III)Cl(2)(dtc-D,L-Pro-Aib(2)-O(t-Bu))] (3b) turned out to be the most effective toward the four human tumor cell lines evaluated (PC3, 2008, C13, and L540), for which the IC(50) values were lower than cisplatin.

Preliminary chemico-biological studies on Ru(III) compounds with S-methyl pyrrolidine/dimethyl dithiocarbamate.

[RuCl(3).nH(2)O] and Na(trans-[RuCl(4)(DMSO)(2)]) were reacted with 1-pyrrolidinedithiocarbamate (PDT), its S-methyl ester (PDTM), and N,N-dimethylcarbamodithioic acid methyl ester (DMDTM) in water or methanol in order to obtain the corresponding Ru(III) derivatives. Once isolated and purified, the complexes were characterized by means of elemental analysis, conductivity measurements, FT-IR and (1)H NMR spectroscopy, ion electrospray mass spectrometry (ESI-MS), and thermal analyses.

Ru(III)-based compounds with sulfur donor ligands: synthesis, characterization, electrochemical behaviour and anticancer activity.

In recent years, Ru(iii) complexes have emerged as a new class of effective anticancer agents against tumors that proved to be resistant to all other chemotherapeutic drugs currently in clinical use. To extend our previous studies on metal complexes containing sulfur-donor ligands, we report here on the synthesis and characterization, by means of several spectroscopic and analytical techniques, some [Ru(RSDT)(3)] and [Ru(2)(RSDT)(5)]Cl complexes with dithiocarbamato ligands derived from methyl/ethyl/tert-butyl esters of sarcosine. Their electrochemical behaviour was also studied by cyclic voltammetry.

Chemical and biological profiles of novel copper(II) complexes containing S-donor ligands for the treatment of cancer.

In the last years, we have synthesized some new platinum(II), palladium(II), gold(I/III) complexes with dithiocarbamato derivatives as potential anticancer drugs, to obtain compounds with superior chemotherapeutic index in terms of increased bioavailability, higher cytotoxicity, and lower side effects than cisplatin. On the basis of the obtained encouraging results, we have been studying the interaction of CuCl2 with methyl-/ethyl-/tert-butylsarcosine-dithiocarbamato moieties in a 1:2 molar ratio; we also synthesized and studied the N,N-dimethyl- and pyrrolidine-dithiocarbamato copper complexes for comparison purposes. The reported compounds have been successfully isolated, purified, and fully characterized by means of several spectroscopic techniques.