Synthesis, structural characterization and cell death-inducing effect of novel palladium(II) and platinum(II) saccharinate complexes with 2-(hydroxymethyl)pyridine and 2-(2-hydroxyethyl)pyridine on cancer cells in vitro

Bioorg Med Chem. 2013 Nov 1;21(21):6427-34. doi: 10.1016/j.bmc.2013.08.050. Epub 2013 Sep 3.

Abstract

Four palladium(II) and platinum(II) saccharinate (sac) complexes with 2-(hydroxymethyl)pyridine (2-hmpy) and 2-(2-hydroxyethyl)pyridine (2-hepy), namely trans-[Pd(2-hmpy)2(sac)2]·H2O (1), trans-[Pt(2-hmpy)2(sac)2]·3H2O (2), trans-[Pd(2-hepy)2(sac)2] (3) and trans-[Pt(2-hepy)2(sac)2] (4), have been synthesized and characterized by elemental analysis, UV-vis, IR and NMR. Single crystal X-ray analysis reveals that the metal(II) ions in each complex are coordinated by two sac and two 2-hmpy or 2-hepy ligands with a trans arrangement. Anticancer effects of 1-4 were tested against four different cancer cell lines (A549 and PC3 for lung cancer, C6 for glioblastoma, and Hep3B for liver cancer). Cytotoxicity was first screened by the MTT assay and the results were further confirmed by the ATP assay. The mode of cell death was determined by both histological and biochemical methods. Among the metal complexes, complex 2 resulted in relatively stronger anti-growth effect in a dose-dependent manner (3.13-200μM), compared to the others, by inducing apoptosis.

Keywords: Apoptosis; Cancer; Cytotoxicity; Palladium(II) and platinum(II) complexes.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / toxicity
  • Apoptosis / drug effects
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Coordination Complexes / chemical synthesis*
  • Coordination Complexes / chemistry
  • Coordination Complexes / toxicity
  • Crystallography, X-Ray
  • Humans
  • Isomerism
  • Keratin-18 / metabolism
  • Molecular Conformation
  • Palladium / chemistry*
  • Pyridines / chemistry*
  • Saccharin / chemistry
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Coordination Complexes
  • Keratin-18
  • Pyridines
  • Palladium
  • Caspase 3
  • Saccharin
  • pyridine