Paraptotic Cell Death as an Unprecedented Mode of Action Observed for New Bipyridine-Silver(I) Compounds Bearing Phosphane Coligands
- Author(s)
- Ricardo G. Teixeira, Alessia Stefanelli, Adhan Pilon, Rebecca Warmers, Xavier Fontrodona, Isabel Romero, Paulo J. Costa, Maria J. Villa de Brito, Xenia Hudec, Christine Pirker, Sebastian Türck, Alexandra M.M. Antunes, Christian R. Kowol, Ingo Ott, Anamaria Brozovic, Andy Sombke, Margret Eckhard, Ana Isabel Tomaz, Petra Heffeter, Andreia Valente
- Abstract
In this work, we investigated the anticancer activity of several novel silver(I) 2,2′-bipyridine complexes containing either triphenylphosphane (PPh3) or 1,2-bis(diphenylphosphino)ethane (dppe) ligands. All compounds were characterized by diverse analytical methods including ESI-MS spectrometry; NMR, UV-vis, and FTIR spectroscopies; and elemental analysis. Moreover, several compounds were also studied by X-ray single-crystal diffraction. Subsequently, the compounds were investigated for their anticancer activity against drug-resistant and -sensitive cancer cells. Noteworthily, neither carboplatin and oxaliplatin resistance nor p53 deletion impacted on their anticancer efficacy. MES-OV cells displayed exceptional hypersensitivity to the dppe-containing drugs. This effect was not based on thioredoxin reductase inhibition, enhanced drug uptake, or apoptosis induction. In contrast, dppe silver drugs induced paraptosis, a novel recently described form of programmed cell death. Together with the good tumor specificity of this compound’s class, this work suggests that dppe-containing silver complexes could be interesting drug candidates for the treatment of resistant ovarian cancer.
- Organisation(s)
- Department of Inorganic Chemistry
- External organisation(s)
- Universidade de Lisboa, Medizinische Universität Wien, Universitat de Girona, Technische Universität Carolo-Wilhelmina zu Braunschweig, Rudjer Boskovic Institute
- Journal
- Journal of Medicinal Chemistry
- Volume
- 67
- Pages
- 6081-6098
- No. of pages
- 18
- ISSN
- 0022-2623
- DOI
- https://doi.org/10.1021/acs.jmedchem.3c01036
- Publication date
- 02-2024
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 301305 Medical chemistry
- ASJC Scopus subject areas
- Molecular Medicine, Drug Discovery
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/2d5bd829-2fd3-4a8c-a28c-d475ad62b6d9