Solvent assisted formation of ruthenium(III) and ruthenium(II) hydrazone complexes in one-pot with potential in vitro cytotoxicity and enhanced LDH, NO and ROS release

Dalton Trans. 2016 Jan 28;45(4):1693-707. doi: 10.1039/c5dt03849a.

Abstract

A set each of new bivalent and trivalent ruthenium complexes, [Ru(III)(HL)Cl2(EPh3)2] and [Ru(II)(L)(CO)(EPh3)2] (E = P (complexes and ) or As (complexes and )) were synthesised from the reactions of [Ru(III)Cl3(EPh3)3] with 2-hydroxynaphthaldehyde benzoic acid hydrazone (H2L) in methanol-chloroform and characterized by elemental analysis, spectral data and XRD study. A suitable mechanism to account for the formation of bivalent ruthenium carbonyl complexes from the corresponding trivalent precursors is provided by considering the role of added base in the reaction. Interaction of complexes with CT-DNA/bovine serum albumin was analysed with absorption and emission spectral titration studies. In vitro cytotoxic potential of the above ruthenium hydrazone complexes assayed against the A549 cell line revealed a significant growth inhibition. The test complexes added in IC50 concentration into the cell culture medium enhanced the release of lactate dehydrogenase, NO and reactive oxygen species in comparison with the control. Cell death induced by the complexes was studied using a propidium iodide staining assay and showed noticeable changes in the cell morphology which resembled apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Chloroform / chemistry
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Hydrazones / chemistry
  • Hydrazones / pharmacology*
  • L-Lactate Dehydrogenase / metabolism*
  • Methanol / chemistry
  • Models, Molecular
  • Molecular Structure
  • Nitric Oxide / metabolism*
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology*
  • Reactive Oxygen Species / metabolism*
  • Ruthenium / chemistry
  • Ruthenium / pharmacology*
  • Solvents / chemistry
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Hydrazones
  • Organometallic Compounds
  • Reactive Oxygen Species
  • Solvents
  • Nitric Oxide
  • Ruthenium
  • Chloroform
  • L-Lactate Dehydrogenase
  • Methanol