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Thiosugar-functionalized gold(I)-NHC complexes as selective anticancer agents for potential targeted therapy.

Ester Giorgi¹, Tarita Biver¹, Michele Mannelli²

¹Department of Chemistry and Industrial Chemistry, University of Pisa, Pisa, Italy.

Frontiers in Chemistry

|March 13, 2026

Summary

Novel gold(I) N-heterocyclic carbene (NHC) complexes were developed. Thiosugar conjugation enhanced cellular uptake and cytotoxicity against ovarian cancer cells, showing improved potency and selectivity.

Keywords:

bioconjugates gold(I)-NHC complexes metal-based drugs ovarian cancer targeting strategies

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Area of Science:

Organometallic Chemistry
Medicinal Chemistry
Cancer Biology

Background:

Gold(I) complexes with N-heterocyclic carbene (NHC) ligands are explored for therapeutic potential.
Strategies to improve cellular uptake and target specificity of metal-based drugs are crucial.

Purpose of the Study:

To synthesize and characterize novel gold(I)-NHC complexes.
To evaluate the impact of thiosugar conjugation and peptide targeting on their anticancer activity.
To assess interaction with human serum albumin (HSA) and cytotoxicity against ovarian cancer cell lines.

Main Methods:

Synthesis and characterization of four gold(I)-NHC complexes, two with thiosugar residues.
Electrospray ionization mass spectrometry (ESI-MS) and fluorescence titrations for HSA interaction.
In vitro cytotoxicity assays on A2780 (sensitive and resistant) and SKOV-3 ovarian cancer cell lines.
Confocal microscopy and fluorescence-activated cell sorting (FACS) for cellular uptake studies.

Main Results:

Thiosugar conjugation significantly enhanced the potency and selectivity of gold(I)-NHC complexes compared to non-conjugated analogs.
Complexes showed varying degrees of interaction with HSA.
Cellular uptake and cytotoxic effects were observed, with thiosugar-modified complexes demonstrating improved efficacy.
Luteinizing hormone-releasing hormone (LHRH) peptide conjugates showed a slight enhancement in cytotoxicity and selectivity.

Conclusions:

Thiosugar conjugation is an effective strategy for enhancing the anticancer properties of gold(I)-NHC complexes.
Targeting peptides, particularly LHRH, may offer modest improvements in cytotoxicity and selectivity.
These findings support the development of novel gold-based therapeutics for ovarian cancer.