Beyond platinum compounds: studies on the potential cytotoxic activity of new coinage metal complexes

The project aims at the synthesis and study of new molecules that could bind different targets with a different mechanism of action compared to classical platinum-based ones. Gold complexes are commonly accounted as thioredoxin reductase inhibitors and binders for other biologically-relevant proteins, but it could be interesting to find gold complexes able to bind also genomic targets, especially non-canonical ones. In this frame, the detailed characterisation of the binding mechanisms considers also the comparison with the Ag(I) complex counterpart. On the other hand, there is still much room for studies on species that are supposed to prefer genomic targets but for which information on the binding to RNAs and non-canonical structures of DNA and RNA like G-quadruplexes, i-motifs and four-way junctions are still missing or incomplete. For this purpose, a comparative study of the effects exerted by the different metal centres and different ligands is crucial to enlighten the metal complexes' behaviour towards the selected biomolecules. The metal complexes currently under investigation can be divided into four groups: diphenyl-(anthracen-9-ylmethyl)phosphine-Au-X where X=Cl, Br, I; two Ag(I) and Au(I) N-heterocyclic bis carbenes; Au(III), Pt(II), and Pd(II) square-planar complexes with tetradentate ligands; 1,10-Phenanthroline/Pd(II) complexes bearing arene ligands with N or O coordinating groups. A biological evaluation of the cytotoxic activity of these compounds has been done during an abroad period at the University of Burgos.