Combining [arene-Ru] with azocarboxamide to generate a complex with cytotoxic properties

Chemistry. 2014 Dec 22;20(52):17296-9. doi: 10.1002/chem.201404448. Epub 2014 Nov 5.

Abstract

Azocarboxamide (azcH) has been combined for the first time with [Ru-Cym] to generate metal complexes with N,N- and N,O-coordination mode, [(Cym)Ru(azc)Cl] and [(Cym)Ru(azcH)Cl](+) [PF6 ](-). Geometric and electronic structures of the complexes are reported along with their in vitro activities against different tumour cell lines and preliminary results on solution chemistry. Compound [(Cym)Ru(azc)Cl] exhibited remarkable cytotoxic properties. It was cell-type specific and had comparable IC50 values towards both cancer cells and their drug-resistant subline. A tenfold increase in the sensitivity towards [(Cym)Ru(azc)Cl] was noted for the tumour cells with depleted intracellular glutathione (GSH) level, suggesting the essential role of GSH in cell response to this compound.

Keywords: N,N ligands; N,O ligands; antitumor agents; azocarboxamide; ruthenium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / toxicity
  • Aza Compounds / chemistry*
  • Cell Line, Tumor
  • Coordination Complexes / chemistry*
  • Coordination Complexes / toxicity
  • Crystallography, X-Ray
  • Glutathione / chemistry*
  • Humans
  • Models, Molecular
  • Ruthenium / chemistry*

Substances

  • Antineoplastic Agents
  • Aza Compounds
  • Coordination Complexes
  • Ruthenium
  • Glutathione