Synthesis, characterization, and cytotoxicity studies of Cu(II), Zn(II), and Fe(III) complexes of N-derivatized 3-hydroxy-4-pyridiones

J Inorg Biochem. 2014 Mar:132:59-66. doi: 10.1016/j.jinorgbio.2013.12.003. Epub 2013 Dec 22.

Abstract

The deleterious role of metal ions in Alzheimer's disease has inspired the study of various metal chelators. We previously showed the synthesis and in vitro activity of several bidentate hydroxypyridinone compounds, including 3-hydroxy-2-methyl-1-phenyl-4(1H)-pyridinone (1), 1-(4-aminophenyl)-3-hydroxy-2-methyl-4(1H)-pyridinone (2), and 1-(2-benzothiazolyl)-3-hydroxy-2-methyl-4(1H)-pyridinone (3). While the focus has been on the Cu(II) ion, the other biorelevant metals, Zn(II) and Fe(III) have been largely neglected. Herein, we report the synthesis of Zn(II) and Fe(III) complexes of ligands 1, 2, and 3, and their characterization by infrared (IR) spectroscopy, high resolution mass spectrometry (HR-MS), elemental analysis, and NMR, where applicable. Solid state structures of Zn(1)2, Fe(1)3, and Cu(3)2 are analyzed with X-ray crystallography. The cytotoxicity of pro-ligands 1, 2, and 3, and the three metal complexes of 2 are examined in a neuronal cell line to determine the effect of metal chelation on toxicity of the compounds.

Keywords: Alzheimer's disease; Copper; Hydroxypyridinone; Iron; Metal complex cytotoxicity; Zinc.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / cytology
  • Cell Line
  • Chelating Agents / chemistry
  • Chelating Agents / toxicity
  • Coordination Complexes / chemical synthesis*
  • Coordination Complexes / chemistry
  • Coordination Complexes / toxicity
  • Copper / chemistry*
  • Iron / chemistry*
  • Ligands
  • Mice
  • Models, Molecular
  • Neurons / drug effects
  • Nitrogen / chemistry
  • Pyridones / chemistry*
  • Pyridones / toxicity*
  • Zinc / chemistry*

Substances

  • Chelating Agents
  • Coordination Complexes
  • Ligands
  • Pyridones
  • Copper
  • Iron
  • Zinc
  • Nitrogen