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Characterization of the binding sites of the anticancer ruthenium(III) complexes KP1019 and KP1339 on human serum albumin via competition studies

  • Orsolya Dömötör
  • Christian G. Hartinger
  • Anna K. Bytzek
  • Tamás Kiss
  • Bernhard K. Keppler
  • Eva A. Enyedy
Original Paper

Abstract

Indazolium trans-[tetrachloridobis(1H-indazole)ruthenate(III)] (KP1019) and its Na+ analogue (KP1339) are two of the most prominent non-platinum antitumor metal complexes currently undergoing clinical trials. After intravenous administration, they are known to bind to human serum albumin (HSA) in a noncovalent manner. To elucidate their HSA binding sites, displacement reactions with the established site markers warfarin and dansylglycine as well as bilirubin were monitored by spectrofluorimetry, ultrafiltration–UV–vis spectrophotometry, and/or capillary zone electrophoresis. Conditional stability constants for the binding of KP1019 and KP1339 to sites I and II of HSA were determined, indicating that both Ru(III) compounds bind to both sites with moderately strong affinity (log K 1′ = 5.3–5.8). No preference for either binding site was found, and similar results were obtained for both metal complexes, demonstrating low influence of the counter ion on the binding event.

Graphical abstract

Keywords

Solution equilibrium Albumin Binding affinity Fluorescence Ruthenium anticancer agents Site markers 

Abbreviations

BGE

Background electrolyte

BR

Bilirubin

CE

Capillary electrophoresis

CZE

Capillary zone electrophoresis

DG

Dansylglycine

HMM

High molecular mass

HSA

Human serum albumin

KP1019

Indazolium trans-[tetrachloridobis(1H-indazole)ruthenate(III)]

KP1339

Sodium trans-[tetrachloridobis(1H-indazole)ruthenate(III)]

LMM

Low molecular mass

NAMI-A

Imidazolium trans-[tetrachlorido(dimethyl sulfoxide)(1H-imidazole)ruthenate(III)]

WF

Warfarin

Notes

Acknowledgments

This work was supported by the Hungarian Research Foundation OTKA K77833 and “TÁMOP-4.2.1/B-09/1/KONV-2010-0005—Creating the Center of Excellence at the University of Szeged,” cofinanced by the European Regional Fund. E.A.E. gratefully acknowledges the financial support from a J. Bolyai Research Fellowship. We thank the Austrian Science Fund (FWF; I496-B11), and COST D39 and CM0902 for financial support.

Supplementary material

775_2012_944_MOESM1_ESM.pdf (560 kb)
Supplementary material (PDF 560 kb)

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Copyright information

© SBIC 2012

Authors and Affiliations

  • Orsolya Dömötör
    • 1
  • Christian G. Hartinger
    • 2
    • 3
  • Anna K. Bytzek
    • 3
  • Tamás Kiss
    • 1
    • 4
  • Bernhard K. Keppler
    • 3
  • Eva A. Enyedy
    • 1
  1. 1.Department of Inorganic and Analytical ChemistryUniversity of SzegedSzegedHungary
  2. 2.School of Chemical SciencesThe University of AucklandAucklandNew Zealand
  3. 3.Institute of Inorganic ChemistryUniversity of ViennaViennaAustria
  4. 4.Bioinorganic Chemistry Research Group of the Hungarian Academy of SciencesUniversity of SzegedSzegedHungary

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