Palladium(II) complexes with N-heteroaromatic bidentate hydrazone ligands: the effect of the chelate ring size and lipophilicity on in vitro cytotoxic activity

Chem Biol Drug Des. 2014 Sep;84(3):333-41. doi: 10.1111/cbdd.12322. Epub 2014 May 12.

Abstract

Novel Pd(II) complex with N-heteroaromatic Schiff base ligand, derived from 8-quinolinecarboxaldehyde (q8a) and ethyl hydrazinoacetate (haOEt), was synthesized and characterized by analytical and spectroscopy methods. The structure of novel complex, as well as structures of its quinoline and pyridine analogues, was optimized by density functional theory calculations, and theoretical data show good agreement with experimental results. A cytotoxic action of the complexes was evaluated on cultures of human promyelocytic leukemia (HL-60), human glioma (U251), rat glioma (C6), and mouse fibrosarcoma (L929) cell lines. Among investigated compounds, only complexes with quinoline-based ligands reduce the cell numbers in a dose-dependent manner in investigated cell lines. The observed cytotoxic effect of two isomeric quinoline-based complexes is predominantly mediated through the induction of apoptotic cell death in HL-60 cell line. The cytotoxicity of most efficient novel Pd(II) complex is comparable to the activity of cisplatin, in all cell lines investigated.

Keywords: X-ray crystallography; apoptosis; biological screening; chemical structure; palladium(II) complexes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Caspases / metabolism
  • Cell Line, Tumor
  • Chelating Agents / chemistry*
  • Coordination Complexes / chemical synthesis
  • Coordination Complexes / chemistry*
  • Coordination Complexes / toxicity
  • Crystallography, X-Ray
  • HL-60 Cells
  • Humans
  • Hydrazones / chemical synthesis
  • Hydrazones / chemistry*
  • Hydrazones / toxicity
  • Hydrophobic and Hydrophilic Interactions
  • Ligands
  • Mice
  • Molecular Conformation
  • Palladium / chemistry*
  • Rats
  • Schiff Bases / chemistry
  • Structure-Activity Relationship

Substances

  • Chelating Agents
  • Coordination Complexes
  • Hydrazones
  • Ligands
  • Schiff Bases
  • Palladium
  • Caspases