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

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

  • J Med Chem. 2024 Feb 24. doi: 10.1021/acs.jmedchem.3c01036.
Ricardo G Teixeira 1,  Alessia Stefanelli 2,  Adhan Pilon 1,  Rebecca Warmers 2,  Xavier Fontrodona 3,  Isabel Romero 3,  Paulo J Costa 4,  Maria J Villa de Brito 1,  Xenia Hudec 2,  Christine Pirker 2,  Sebastian Türck 5,  Alexandra M M Antunes 6,  Christian R Kowol 7,  Ingo Ott 5,  Anamaria Brozovic 8,  Andy Sombke 9,  Margret Eckhard 9,  Ana Isabel Tomaz 1,  Petra Heffeter 2,  Andreia Valente 1
Affiliations

Affiliations

  • 1 Centro de Química Estrutural, Institute of Molecular Sciences, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, Lisboa 1749-016, Portugal.
  • 2 Center for Cancer Research and Comprehensive Cancer Center, Medical University of Vienna, Vienna 1090, Austria.
  • 3 Departament de Química and Serveis Tècnics de Recerca, Universitat de Girona, Campus de Montilivi, Girona 17071, Spain.
  • 4 BioISI - Instituto de Biosistemas e Ciências Integrativas, Faculdade de Ciências, Universidade de Lisboa, Lisboa 1749-016, Portugal.
  • 5 Institute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig, Beethovenstr. 55, Braunschweig 38106, Germany.
  • 6 Centro de Química Estrutural (CQE), Institute of Molecular Sciences, Departamento de Engenharia Química, Instituto Superior Técnico (IST), Universidade de Lisboa, Av Rovisco Pais 1, Lisboa 1049-001, Portugal.
  • 7 Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Waehringerstrasse 42, Vienna 1090, Austria.
  • 8 Division of Molecular Biology, Ruđer Bošković Institute, Bijenička cesta 54,Zagreb 10000, Croatia.
  • 9 Center for Anatomy and Cell Biology, Cell and Developmental Biology, Medical University of Vienna, Schwarzspanierstraße 17, Vienna 1090, Austria.
PMID: 38401050 DOI: 10.1021/acs.jmedchem.3c01036
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.

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