Synthesis of new allyl palladium complexes bearing purine-based NHC ligands with antiproliferative and proapoptotic activities on human ovarian cancer cell lines

Dalton Trans. 2018 Oct 2;47(38):13616-13630. doi: 10.1039/c8dt01831f.

Abstract

A series of new palladium allyl complexes bearing purine-based carbenes derived from caffeine, theophylline and theobromine have been prepared and characterized by NMR spectroscopy, and elemental analysis and in two cases by single crystal X-ray diffraction. The cytotoxic and proapoptotic activities of compounds have been determined in vitro on human ovarian cancer A2780 and SKOV-3 cell lines. These experiments have shown that the palladium-allyl fragment induces a general cytotoxicity, but the choice of the supporting ligands is of paramount importance for achieving the best results. In particular complexes 4c, 4d and 5d exhibit a higher antiproliferative effect (IC50: 0.09, 0.81 and 0.85 μM respectively) than cisplatin (IC50: 1.5 μM) on A2780 cells, and 4d (IC50: 1.7 μM vs. 5.94 μM) on SKOV-3 cell line. Moreover in many cases it has been proved that the cytotoxicity of our complexes is associated with the induction of apoptosis.

MeSH terms

  • Alkenes / chemistry
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chemistry Techniques, Synthetic
  • Female
  • Heterocyclic Compounds / chemistry
  • Humans
  • Inhibitory Concentration 50
  • Ligands
  • Methane / analogs & derivatives*
  • Methane / chemistry
  • Organometallic Compounds / chemical synthesis*
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology*
  • Ovarian Neoplasms / pathology*
  • Palladium / chemistry*
  • Purines / chemistry*

Substances

  • Alkenes
  • Antineoplastic Agents
  • Heterocyclic Compounds
  • Ligands
  • Organometallic Compounds
  • Purines
  • carbene
  • Palladium
  • Methane