Paraptotic Cell Death as an Unprecedented Mode of Action Observed for New Bipyridine-Silver(I) Compounds Bearing Phosphane Coligands

Teixeira, Ricardo G.; Stefanelli, Alessia; Pilon, Adhan; Warmers, Rebecca; Fontrodona, Xavier; Romero, Isabel; Costa, Paulo J.; Villa de Brito, Maria J.; Hudec, Xenia; Pirker, Christine; Türck, Sebastian; Antunes, Alexandra M. M.; Kowol, Christian R.; Ott, Ingo; Brozović, Anamaria; Sombke, Andy; Eckhard, Margret; Tomaz, Ana Isabel; Heffeter, Petra; Valente, Andreia (2024) Paraptotic Cell Death as an Unprecedented Mode of Action Observed for New Bipyridine-Silver(I) Compounds Bearing Phosphane Coligands. Journal of Medicinal Chemistry, 67 (8). pp. 6081-6098. ISSN 0022-2623

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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.

Item Type:	Article
Uncontrolled Keywords:	ovarian cancer; cell death; bipyridine-silver(I) compounds; drug resistance; phosphane coligands
Subjects:	NATURAL SCIENCES > Chemistry
Divisions:	Division of Molecular Biology
Depositing User:	Ivana Vuglec
Date Deposited:	25 Mar 2026 09:41
URI:	http://fulir.irb.hr/id/eprint/11426
DOI:	10.1021/acs.jmedchem.3c01036

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