Copper pyrithione complexes with endoplasmic reticulum localisation showing anticancer activity <i>via</i> ROS generation
Copper complexes have great potential to overcome the disadvantages of platinum-based anticancer agents, owing to their lower systemic toxicity. Copper pyrithione showed early promise as an anticancer candidate, but further studies have not been forthcoming. Herein, we report a series of copper pyrithione derivatives that show between 1 and 2 orders of magnitude higher activity than cisplatin against pancreatic and breast cancer cell lines, along with good selectivity over healthy cells. Reactive oxygen species (ROS) generation is determined to be a likely mode of action. A fluorescent analogue shows localisation in the endoplasmic reticulum of cells, which is highly unusual for metal-based therapeutics and opens up the potential for unique modes of therapeutic action.
Authors
- Dominic J. Black (ORCID: https://orcid.org/0000-0003-0804-4860)
- Benjamin J. Hofmann (ORCID: https://orcid.org/0000-0001-6408-3472)
- Karrera Y. Djoko (ORCID: https://orcid.org/0000-0001-9814-6515)
- Jennifer M. Hunter (ORCID: https://orcid.org/0000-0002-1993-6410)
- Róbert Pál (ORCID: https://orcid.org/0000-0002-0641-4218)
- Tameryn Stringer (ORCID: https://orcid.org/0000-0002-4439-131X)
- James W. Walton (ORCID: https://orcid.org/0000-0002-8482-6285)
- Rianne M. Lord (ORCID: https://orcid.org/0000-0001-9981-129X)
- Atreyee Mishra
- Thomas. S. Bradford (ORCID: https://orcid.org/0009-0009-2623-2225)
- Harvey J Smart (ORCID: https://orcid.org/0000-0002-1460-0782)
Institutions
- University of East Anglia (GB)
- Durham University (GB)
- University of Warwick (GB)
- University of Waikato (NZ)
Publication Details
- Journal
- Chemical Science
- Published
- 2025-01-01
- DOI
- https://doi.org/10.1039/d4sc06628f
- Citations
- 1
- Primary Topic
- Metal complexes synthesis and properties
- Type
- article
- Field-Weighted Citation Impact
- 1.05
Funders
- University of Warwick
- Durham University
- Medical Research Council
- Engineering and Physical Sciences Research Council