Auranofin, a gold(I)-based
complex, is under clinical
trials for
application as an anticancer agent for the treatment of nonsmall-cell
lung cancer and ovarian cancer. In the past years, different derivatives
have been developed, modifying gold linear ligands in the search for
new gold complexes endowed with a better pharmacological profile.
Recently, a panel of four gold(I) complexes, inspired by the clinically
established compound auranofin, was reported by our research group.
As described, all compounds possess an [Au{P(OMe)3}]+cationic moiety, in which the triethylphosphine of the parent
compound auranofin was replaced with an oxygen-rich trimethylphosphite
ligand. The gold(I) linear coordination geometry was complemented
by Cl–, Br–, I–, and the auranofin-like thioglucose tetraacetate ligand. As previously
reported, despite their close similarity to auranofin, the panel compounds
exhibited some peculiar and distinctive features, such as lower logPvalues which can induce relevant differences in the overall
pharmacokinetic profiles. To get better insight into the P–Au
strength and stability, an extensive study was carried out for relevant
biological models, including three different vasopressin peptide analogues
and cysteine, using31P NMR and LC-ESI-MS. A DFT computational
study was also carried out for a better understanding of the theoretical
fundamentals of the disclosed differences with regard to triethylphosphine
parent compounds.