[PDF] Caffeine-based gold(I) N-heterocyclic carbenes as possible anticancer agents: synthesis and biological properties. | Semantic Scholar (2024)

Mechanistic information on the system derived from biotin-conjugated iodoacetamide assays showed selective metal binding to selenocysteine residues, and preliminary confocal fluorescence microscopy experiments proved that 3 enters tumor cells, where it reaches the nuclear compartment.

Pt(II)–NHC complexes form 5′-guanosine monophosphate adducts under physiologically relevant conditions and interact with plasmid DNA in contrast to their Au(I) analogs, corroborating their distinct modes of action.

It is highlighted that coordination of two carbene ligands to the same gold(I) center greatly enhances the antiproliferative effects of the resulting compound in comparison to the monocarbene derivative.

The rhodium(i) NHC derivative represents a multi-target compound with promising anti-cancer potential and acted as both a mammalian and an E. coli thioredoxin reductase inhibitor.

For the first time C^N cyclometallated gold(III) complexes were shown to be potent inhibitors of the zinc finger protein PARP-1, involved in the mechanism of cisplatin resistance.

In order to gain insight into the mechanism of biological action of the gold compounds, their effect on the pivotal cellular target seleno-enzyme thioredoxin reductase (TrxR), involved in the maintenance of intracellular redox balance, was investigated in depth.

The mixed AuI NHC complex, (tert‐butylethynyl)‐1,3‐bis‐(2,6‐diisopropylphenyl)imidazol‐2‐ylidene gold(I), bearing an alkynyl moiety as ancillary ligand, showed high cytotoxicity in cancer cells in vitro, while being barely toxic in healthy rat kidney tissues.

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The compounds showed potent and selective TrxR inhibition properties in particular in cancer cell lines, and induced extensive oxidation of thioredoxins (Trxs), which was more relevant in the cancerous cells than in HEK-293T cells.

Investigation of gold(I) complexes with benzimidazole derived N-heterocyclic carbene (NHC) ligands represent a promising class of gold coordination compounds with a good stability against the thiol glutathione.

Remarkable antiproliferative effects, a strong induction of apoptosis, and enhancement of reactive oxygen species (ROS) formation as well as other effects on tumor cell metabolism confirmed the promising potential of the complexes as novel anticancer chemotherapeutics.

Both gold and silver complexes lead to oxidation of the thioredoxin system, the silver(I) derivative being particularly effective, and the dimerization of peroxiredoxin 3 was also observed, demonstrating the ability of these compounds to reach the mitochondrial target.

The enhanced stabilization of the gold(III) ion and the ease of structural modification render porphyrins an attractive ligand system in the development of physiologically stable gold( III) complexes with anticancer and anti-angiogenic activities.

The state of the art of preclinical studies on anticancer gold compounds, carried out either in vitro or in vivo, are defined and the overall perspectives on the development of gold compounds as effective anticancer drugs with an innovative mechanism of action are critically discussed.

This Perspective summarizes the results obtained for different families of bioactive organometallic gold compounds including cyclometallated gold(iii) complexes with C,N-donor ligands, gold( I) and gold(I/III) N-heterocyclic (NHC) carbene complexes, as well asgold(I) alkynyl complexes, with promising anticancer effects.

This review describes the advances that have been achieved in using transition metal complexes containing NHC ligands as antitumor agents and clearly demonstrate the great potential of metal-NHC complexes as antitUMor agents.

This review defines the possible modes of action and the most probable biomolecular targets for a few representative gold compounds on which extensive biochemical and cellular data have been gathered and focuses on auranofin and analogues, on gold( III) porphyrins and gold(III) dithiocarbamates.

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