Ni(II), Cu(II), and Zn(II) diethyldithiocarbamate complexes show various activities against the proteasome in breast cancer cells

J Med Chem. 2008 Oct 23;51(20):6256-8. doi: 10.1021/jm8007807. Epub 2008 Sep 25.

Abstract

A series of three complexes with diethyldithiocarbamate ligand and three different metals (Ni, Cu, Zn) was prepared, confirmed by X-ray crystallography, and tested in human breast cancer MDA-MB-231 cells. Zinc and copper complexes, but not nickel complex, were found to be more active against cellular 26S proteasome than against purified 20S proteasome core particle. One of the possible explanations is inhibition of JAMM domain in the 19S proteasome lid.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Copper
  • Ditiocarb / analogs & derivatives*
  • Ditiocarb / chemistry
  • Ditiocarb / pharmacology*
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Molecular Structure
  • Nickel
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology*
  • Proteasome Endopeptidase Complex / metabolism
  • Proteasome Inhibitors*
  • Zinc

Substances

  • Enzyme Inhibitors
  • Organometallic Compounds
  • Proteasome Inhibitors
  • bis(N,N-diethyldithiocarbamate)Cu (II) complex
  • Copper
  • Nickel
  • Ditiocarb
  • Proteasome Endopeptidase Complex
  • Zinc