Four novel gold(I) N-heterocyclic carbene (NHC) complexes were synthesized and characterized; they are tuned in terms of the aromatic extension of the NHC scaffold and two of them contain a thiosugar residue to enhance their cellular uptake. To verify their potential interaction with human serum albumin (HSA), ESI-MS interaction analysis and fluorescence titrations were performed. Biological studies were carried out to evaluate their possible cytotoxic effect on three ovarian cancer cell lines, i.e., A2780 (both sensitive and cisplatin-resistant), and SKOV-3. Confocal microscopy and fluorescence-activated cell sorting tests were also carried out for the four complexes. Thiosugar conjugation proved to be an effective strategy to enhance potency and selectivity, resulting in a considerable improvement compared to the corresponding complexes lacking the thiosugar moiety. Furthermore, six bioconjugates containing targeting peptides were synthesized; in most cases, no significant improvement in either cytotoxic activity or selectivity was observed, except for the LHRH peptide conjugates, which showed a slight enhancement in both cytotoxicity and selectivity compared to the unconjugated complexes.
Giorgi et al. (Wed,) studied this question.