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: Chemistry - A European Journal

T. Scattolin, E. Bortolamiol, F. Visentin, S. Palazzolo, I. Caligiuri, T. Perin, V. Canzonieri, N. Demitri, F. Rizzolio, A. Togni

Research output: Contribution to journalArticlepeer-review

Abstract

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. © 2020 Wiley-VCH GmbH
Original languageEnglish
Pages (from-to)11868-11876
Number of pages9
JournalChem. Eur. J.
Volume26
Issue number51
DOIs
Publication statusPublished - 2020

Keywords

  • allylation
  • N-trifluoromethyl N-heterocyclic carbenes
  • organoids
  • ovarian cancer
  • palladium allyl complexes
  • Diseases
  • Organometallics
  • Synthesis (chemical)
  • Anti-cancer agents
  • Anti-tumor activities
  • Antiproliferative agents
  • Mechanism of action
  • N-heterocyclic carbenes
  • Nucleophilic attack
  • Organometallic compounds
  • Palladium complexes
  • Palladium compounds
  • antineoplastic agent
  • cisplatin
  • coordination compound
  • ligand
  • palladium
  • cell proliferation
  • chemistry
  • drug effect
  • female
  • human
  • ovary tumor
  • pathology
  • tumor cell line
  • Antineoplastic Agents
  • Cell Line, Tumor
  • Cell Proliferation
  • Cisplatin
  • Coordination Complexes
  • Female
  • Humans
  • Ligands
  • Ovarian Neoplasms
  • Palladium

Fingerprint Dive into the research topics of '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: Chemistry - A European Journal'. Together they form a unique fingerprint.

Cite this