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Palladium(II)-η3 -Allyl Complexes Bearing N-Trifluoromethyl N-Heterocyclic Carbenes: A New Generation of Anticancer Agents that Restrain the Growth of High-Grade Serous Ovarian Cancer Tumoroids.
Journal article

Palladium(II)-η3 -Allyl Complexes Bearing N-Trifluoromethyl N-Heterocyclic Carbenes: A New Generation of Anticancer Agents that Restrain the Growth of High-Grade Serous Ovarian Cancer Tumoroids.

  • Scattolin T Department of Chemistry and Centre for Sustainable Chemistry, Ghent University, Krijgslaan 281,S-3, 9000, Ghent, Belgium.
  • Bortolamiol E Department of Molecular Sciences and Nanosystems, Università Ca' Foscari, Campus Scientifico Via Torino 155, 30174, Venezia-Mestre, Italy.
  • Visentin F Department of Molecular Sciences and Nanosystems, Università Ca' Foscari, Campus Scientifico Via Torino 155, 30174, Venezia-Mestre, Italy.
  • Palazzolo S Pathology Unit, Department of Molecular Biology and Translational Research, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, via Franco Gallini 2, 33081, Aviano, Italy.
  • Caligiuri I Pathology Unit, Department of Molecular Biology and Translational Research, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, via Franco Gallini 2, 33081, Aviano, Italy.
  • Perin T Pathology Unit, Department of Molecular Biology and Translational Research, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, via Franco Gallini 2, 33081, Aviano, Italy.
  • Canzonieri V Pathology Unit, Department of Molecular Biology and Translational Research, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, via Franco Gallini 2, 33081, Aviano, Italy.
  • Demitri N Elettra-Sincrotrone Trieste, S.S. 14 Km 163.5, Area Science Park Basovizza, 34149, Trieste, Italy.
  • Rizzolio F Department of Molecular Sciences and Nanosystems, Università Ca' Foscari, Campus Scientifico Via Torino 155, 30174, Venezia-Mestre, Italy.
  • Togni A Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, ETH Zürich, Vladimir-Prelog-Weg 2, 8093, Zürich, Switzerland.
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  • 2020-05-06
Published in:
  • Chemistry (Weinheim an der Bergstrasse, Germany). - 2020
N-trifluoromethyl N-heterocyclic carbenes
allylation
organoids
ovarian cancer
palladium allyl complexes
Antineoplastic Agents
Cell Line, Tumor
Cell Proliferation
Cisplatin
Coordination Complexes
Female
Humans
Ligands
Ovarian Neoplasms
Palladium
English The first palladium organometallic compounds bearing N-trifluoromethyl N-heterocyclic carbenes have been synthesized. These η3 -allyl complexes are potent antiproliferative agents against different cancer lines (for the most part, IC50 values fall in the range 0.02-0.5 μm). By choosing 1,3,5-triaza-7-phosphaadamantane (PTA) as co-ligand, we can improve the selectivity toward tumor cells, whereas the introduction of 2-methyl substituents generally reduces the antitumor activity slightly. A series of biochemical assays, aimed at defining the cellular targets of these palladium complexes, has shown that mitochondria are damaged before DNA, thus revealing a behavior substantially different from that of cisplatin and its derivatives. We assume that the specific mechanism of action of these organometallic compounds involves nucleophilic attack on the η3 -allyl fragment. The effectiveness of a representative complex, 4 c, was verified on ovarian cancer tumoroids derived from patients. The results are promising: unlike carboplatin, our compound turned out to be very active and showed a low toxicity toward normal liver organoids.
Language
  • English
Open access status
closed
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Persistent URL
https://sonar.ch/global/documents/139903
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