Synthesis, chemical characterization and cancer cell growth-inhibitory activities of Cu(ii) and Ru(iii) aliphatic and aromatic dithiocarbamato complexes

Abstract

In this paper, we focused on the analysis of the effects mediated by different cyclic dithiocarbamic ligands (DTC) on three classes of antiproliferative coordination compounds, namely, Ru(III) complexes with the general formulae [Ru(DTC)₃] and [Ru₂(DTC)₅]Cl, and the neutral Cu(II) derivatives of the type [Cu(DTC)₂]. In particular, we present the synthesis and characterization of a library of total 23 coordination compounds containing Ru(III) or Cu(II) as the biologically-active metal center and two or more dithiocarbamato (DTC) ligands derived from cyclic amines (aliphatic or aromatic). Several techniques including elemental analysis, X-ray crystallography, ESI-MS, ¹H-NMR spectroscopy, FT-IR and UV-Vis spectrophotometry were used to characterize the compounds, which highlighted the different electronic behaviors generated by the substituents within the DTC moiety. Moreover, the synthesized compounds were tested for their stability in order to investigate their antiproliferative activity against 3 human cancer cell lines, namely, HeLa, HepG2 and HepG2/SB3. In particular, HepG2/SB3 was chosen for its aggressiveness due to upregulation of the anti-apoptotic protein SerpinB3. Finally, the most promising compounds are studied in terms of log P. Overall, the results reveal the drug-likeness of some of the derivatives of copper(II) and ruthenium(III).