Elucidation of the interactions of an anticancer ruthenium complex in clinical trials with biomolecules utilizing capillary electrophoresis hyphenated to inductively coupled plasma-mass spectrometry. Short communication

Chem Biodivers. 2008 Aug;5(8):1609-1614. doi: 10.1002/cbdv.200890148.

Abstract

The application of capillary electrophoresis (CE) combined with highly sensitive inductively-coupled-plasma mass spectrometric (ICP-MS) detection allows the interactions of metal complexes with biomolecules to be characterized. This technique has been used to provide new insights into the mode of action of the ruthenium-based anticancer drug candidate indazolium [trans-tetrachlorobis(1H-indazole)ruthenate(III)] (KP1019). While the compound binds rapidly and efficiently to serum proteins, especially albumin, its reactivity towards the model DNA compound 2'-deoxyguanosine 5'-monophosphate (5'-dGMP) is moderate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / blood
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Binding Sites
  • Clinical Trials as Topic
  • DNA / chemistry
  • Deoxyguanine Nucleotides / chemistry
  • Electrophoresis, Capillary / methods*
  • Humans
  • Indazoles / blood
  • Indazoles / chemistry*
  • Indazoles / pharmacology
  • Mass Spectrometry / methods*
  • Molecular Conformation
  • Organometallic Compounds
  • Ruthenium Compounds / blood
  • Ruthenium Compounds / chemistry*
  • Ruthenium Compounds / pharmacology
  • Serum Albumin / chemistry*
  • Spectrophotometry, Ultraviolet
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Deoxyguanine Nucleotides
  • Indazoles
  • Organometallic Compounds
  • Ruthenium Compounds
  • Serum Albumin
  • indazolium trans-(tetrachlorobis(1H-indazole)ruthenate (III))
  • 2'-deoxyguanosine 5'-phosphate
  • DNA