Synthesis and in-depth studies on the anticancer activity of novel palladacyclopentadienyl complexes stabilized by N-Heterocyclic carbene ligands

Thomas Scattolin, Isabella Caligiuri, Nayla Mouawad, Maguie El Boustani, Nicola Demitri, Flavio Rizzolio, Fabiano Visentin

Research output: Contribution to journalArticlepeer-review

Abstract

New palladacyclopentadienyl complexes with bis-N-heterocyclic carbenes as spectator ligands have been synthesized and exhaustively characterized. The crystal structure of complex 1a has been also determined by X-ray diffraction analysis. Their in vitro cytotoxicity and that of other palladacyclopentadienyl derivatives coordinating different ancillary ligands has been determined against different cancer cell lines. Many complexes have shown an antiproliferative activity toward tumor cells often definitely better than cisplatin, whereas they have resulted practically inactive against the non-cancer MRC-5 cell line. The mechanism of action of bis-NHC derivative 1a, particularly active against ovarian cancer cell lines was studied in depth. Through a longitudinally analysis, it is shown that compound 1a induces apoptosis via DNA damage and release of cytochrome C. We propose compound 1a as a powerful and specific drug for the therapy of a deadly disease such as high grade serous ovarian cancer.

Original languageEnglish
Pages (from-to)325-334
Number of pages10
JournalEuropean Journal of Medicinal Chemistry
Volume179
DOIs
Publication statusPublished - Oct 1 2019

Keywords

  • DNA damage
  • N-Heterocyclic carbenes
  • Organometallic anticancer agents
  • Ovarian cancer
  • Palladacyclopentadienyl compounds

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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