Trans-Pd(II) complexes: A different approach for the development of promising anticancer drugs

Pd(II) complexes, thanks to the similarity of their coordination chemistry to that of Pt(II) compounds and their improved solubility in water than the latter, offer a promising way for the design of novel anticancer agents. Considering that trans-Pd(II) complexes are more cytotoxic than their cis-counterparts and endowing them with ligands that could grant them improved stabilization during their circulation inside the body, a panel of trans-Pd(II) complexes with general formula trans-PdL2X2 (where L = pyridine or piperidine, X = Cl, Br, I) was synthesized. The interactions of these complexes with model proteins were studied with UV–vis and NMR spectroscopy, and their in vitro activity against selected cancer cell lines was also investigated. The study demonstrates that square-planar trans-Pd(II) complexes have potential as chemical tools in medicinal chemistry. They are able to interact with proteomic targets, and despite their limited cytotoxic activity towards the selected tumor cell lines, the interaction profiles and solution reactivity provide valuable mechanistic insights on the mode of action of this class of compounds. Indeed, a reproducible and accessible methodology was defined to investigate the square-planar trans-Pd(II) complexes.