New dinuclear palladium(II) complexes with benzodiazines as bridging ligands: interactions with CT-DNA and BSA, and cytotoxic activity

J Biol Inorg Chem. 2019 Oct;24(7):1009-1022. doi: 10.1007/s00775-019-01695-w. Epub 2019 Aug 5.

Abstract

Three new dinuclear Pd(II) complexes with general formula [{Pd(en)Cl}2(μ-L)](NO3)2 [L is bridging ligand quinoxaline (Pd1), quinazoline (Pd2) and phthalazine (Pd3)] were synthesized and characterized by elemental microanalyses, UV-Vis, IR and NMR (1H and 13C) spectroscopy. The interaction of dinuclear Pd1-Pd3 complexes with calf thymus DNA (CT-DNA) has been monitored by viscosity measurements, UV-Vis and fluorescence emission spectroscopy in aqueous phosphate buffer solution (PBS) at pH 7.40 and 37 °C. In addition, these experimental conditions have been applied to investigate the binding affinities of Pd1-Pd3 complexes to the bovine serum albumin (BSA) by fluorescence emission spectroscopy. In vitro antiproliferative and apoptotic activities of the dinuclear Pd(II) complexes have been tested on colorectal and lung cancer cell lines. All tested Pd(II) complexes had lower cytotoxic effect than cisplatin against colorectal cancer cells, but also had similar or even higher cytotoxicity than cisplatin against lung cancer cells. All complexes induced apoptosis of colorectal and lung cancer cells, while the highest antiproliferative effect exerted Pd2 complex.

Keywords: BSA interaction; Cytotoxic activity; DNA interaction; Dinuclear palladium(II) complexes; Spectroscopic characterization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • DNA / metabolism*
  • Heterocyclic Compounds / chemistry*
  • Humans
  • Ligands
  • Models, Molecular
  • Molecular Conformation
  • Organometallic Compounds / chemistry*
  • Organometallic Compounds / metabolism
  • Organometallic Compounds / pharmacology*
  • Palladium / chemistry*
  • Serum Albumin, Bovine / metabolism*

Substances

  • Antineoplastic Agents
  • Heterocyclic Compounds
  • Ligands
  • Organometallic Compounds
  • Serum Albumin, Bovine
  • Palladium
  • DNA
  • calf thymus DNA