Thiosugar-functionalized gold(I)-NHC complexes as selective anticancer agents for potential targeted therapy
Ester Giorgi, Tarita Biver, Michele Mannelli, Tania Gamberi, Matteo Becatti, Giuseppina Sabatino, Elisa Peroni, Olivier Monasson, Damiano Cirri, Chiara Gabbiani, Alessandro Pratesi
TL;DR
Researchers developed gold-based compounds with a sugar-like structure that show improved cancer cell targeting and effectiveness.
Contribution
Thiosugar modification enhances potency and selectivity of gold(I)-NHC complexes for anticancer therapy.
Findings
Thiosugar-functionalized complexes showed higher cytotoxicity and selectivity in ovarian cancer cells.
LHRH peptide conjugates slightly improved activity and selectivity compared to non-conjugated complexes.
Bioconjugates with other targeting peptides did not significantly enhance performance.
Abstract
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…
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Taxonomy
TopicsN-Heterocyclic Carbenes in Organic and Inorganic Chemistry · Metal complexes synthesis and properties · Click Chemistry and Applications