Conférence Enrico FALCONE

Professeur Enrico FALCONE

University of Nottingham

Copper ligands for biomedical applications: from luminescent sensors to anticancer drugs.

Copper (Cu) is an essential element for most organisms, where it is mainly required as redox cofactor in enzymes. However, excess Cu turns out to be toxic through different mechanisms. As a result, Cu dyshomeostasis is involved in several diseases, spanning from genetic disorders of Cu transports, e.g. Menkes (MD) and Wilson’s (WD) diseases, to Alzheimer’s disease (AD) and cancer.

Since the identification of serum labile Cu as a diagnostic marker for WD and AD, convenient methods to measure this specific Cu pool in blood serum are sought.¹ To this end, we developed luminescent probes based on Cu-binding peptides and lanthanide complexes for the selective detection of Cu in biological media.²

Besides, altered Cu metabolism in tumours is gaining interest as a target of new anticancer approaches.³ To get insights into their mode of action, we investigated the reactivity of anticancer Cu-thiosemicarbazone complexes towards relevant biomolecules such as glutathione, finding significant correlations between their redox activity (ROS production) and the previously reported cytotoxicity.^4,5

References

1. Squitti et al, J. Trace Elem. Med. Biol., 2018, 45, 181–188.
2. Falcone et al, Chem. Commun., 2020, 56, 4797–4800.
3. Shanbhag et al, Biochim. Biophys. Acta – Mol. Cell Res., 2021, 1868, 118893.
4. Falcone, Ritacca et al, J. Am. Chem. Soc., 2022, 144, 14758–14768.
5. Ritacca, Falcone et al, Inorg. Chem., 2023, 62, 3957–3964.