ORIGINAL RESEARCH article
Front. Chem.
Sec. Chemical Biology
Thiosugar-Functionalized Gold(I)-NHC Complexes as Selective Anticancer Agents for Potential Targeted Therapy
Ester Giorgi 1
Tarita Biver 1
Michele Mannelli 2
Tania Gamberi 2
Matteo Becatti 2
Giuseppina Sabatino 3
Elisa Peroni 4,5
Olivier Monasson 4,5
Damiano Cirri 1
Chiara Gabbiani 1
Alessandro Pratesi 1
1. Department of Chemistry and Industrial Chemistry, University of Pisa, Pisa, Italy
2. Universita degli Studi di Firenze Dipartimento di Scienze Biomediche Sperimentali e Cliniche Mario Serio, Florence, Italy
3. Istituto di Cristallografia Consiglio Nazionale delle Ricerche Sede di Catania, Catania, Italy
4. CY Cergy Paris Universite, Cergy-Pontoise, France
5. Université Paris-Saclay, Orsay, France
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Abstract
Four novel gold(I) N-heterocyclic carbene (NHC) complexes were synthesized and characterized; they are tuned as for the aromatic extension of the NHC part and two of them contain a thiosugar residue to foster 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 improvements in cytotoxic activity or selectivity were observed, except for the LHRH peptide conjugates, which showed a slight enhancement in both cytotoxicity and selectivity compared to the unconjugated complexes.
Summary
Keywords
Bioconjugates, Gold(I)-NHC complexes, Metal-based drugs, ovarian cancer, Targeting strategies
Received
13 October 2025
Accepted
23 January 2026
Copyright
© 2026 Giorgi, Biver, Mannelli, Gamberi, Becatti, Sabatino, Peroni, Monasson, Cirri, Gabbiani and Pratesi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Alessandro Pratesi
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