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

Thomas Scattolin, Enrica Bortolamiol, Fabiano Visentin, Stefano Palazzolo, Isabella Caligiuri, Tiziana Perin, Vincenzo Canzonieri, Nicola Demitri, Flavio Rizzolio, Antonio 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.

Original languageEnglish
Pages (from-to)11868-11876
Number of pages9
JournalChemistry - A European Journal
Volume26
Issue number51
DOIs
Publication statusPublished - Sep 10 2020

Keywords

  • allylation
  • N-trifluoromethyl N-heterocyclic carbenes
  • organoids
  • ovarian cancer
  • palladium allyl complexes

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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