Towards Copper(I) Clusters for Photo-Induced Oxidation of Biological Thiols in Living Cells

The cell redox balance can be disrupted by the oxidation of biological peptides, eventually leading to cell death, which provides opportunities to develop cytotoxic drugs. With the aim of developing compounds capable of specifically inducing fatal redox reactions upon light irradiation, we have deve...

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Bibliographic Details
Published in:Chembiochem : a European journal of chemical biology 2023-12, Vol.24 (23), p.e202300496-e202300496
Main Authors: Gourdon-Grünewaldt, Lisa, Blacque, Olivier, Gasser, Gilles, Cariou, Kevin
Format: Article
Language:English
Subjects:
Amino acids
Animals
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Antineoplastic drugs
Antitumor agents
Biological activity
Cancer
Cell death
Chemical Sciences
Clusters
Colorectal carcinoma
Copper
Copper - chemistry
Copper compounds
Cysteine - chemistry
Cytotoxicity
Drug development
Humans
Irradiation
Light irradiation
Medicinal Chemistry
Mice
Oxidation
Oxidation-Reduction
Peptides
Photooxidation
Radiation
Redox reactions
Sulfhydryl Compounds - chemistry
Thiols
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Summary:The cell redox balance can be disrupted by the oxidation of biological peptides, eventually leading to cell death, which provides opportunities to develop cytotoxic drugs. With the aim of developing compounds capable of specifically inducing fatal redox reactions upon light irradiation, we have developed a library of copper compounds. This metal is abundant and considered essential for human health, making it particularly attractive for the development of new anticancer drugs. Copper(I) clusters with thiol ligands (including 5 novel ones) have been synthesized and characterized. Structures were elucidated by X-ray diffraction and showed that the compounds are oligomeric clusters. The clusters display high photooxidation capacity towards cysteine - an essential amino acid - upon light irradiation in the visible range (450 nm), while remaining completely inactive in the dark. This photoredox activity against a biological thiol is very encouraging for the development of anticancer photoredox drugs.The in vitro assay on murine colorectal cancer cells (CT26) did not show any toxicity - whether in the dark or when exposed to 450 nm light, likely because of the poor solubility of the complexes in biological medium.
ISSN:1439-4227
1439-7633
DOI:10.1002/cbic.202300496