4.7 Article

2,2′-Bipyridinebutyldithiocarbamatoplatinum(II) and palladium(II) complexes: Synthesis, characterization, cytotoxicity, and rich DNA-binding studies

Journal

BIOORGANIC & MEDICINAL CHEMISTRY
Volume 16, Issue 21, Pages 9616-9625

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2008.08.021

Keywords

DNA binding; Cytotoxicity; Platinum complex; Palladium complex

Funding

  1. Research Council of University of Sistan
  2. Baluchestan
  3. University of Tehran

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Butyldithiocarbamate sodium salt (Bu-dtcNa) and its two complexes, [M(bpy)(Bu-dtc)]NO3 (M = Pt(II) or Pd(II) and bpy = 2,2 '-bipyridine), have been synthesized and characterized on the basis of elemental analysis, molar conductivities, IR, H-1 NMR, and UV-vis spectra. In these complexes, the dithiocarbamato ligand coordinates to Pt(II) or Pd(II) center as bidentate with two sulfur atoms. These complexes show 50% cytotoxic concentration (Cc(50)) values against chronic myelogenous leukemia cell line, K562, much lower than that of cisplatin. The interaction of these complexes with calf thymus DNA was extensively investigated by a variety of spectroscopic techniques. These studies showed that both complexes presumably intercalate in DNA. UV-vis studies imply that they cooperatively bind with DNA and unexpectedly denature the DNA at very low concentrations (similar to 100 mu L). Palladium complex breaks the DNA into two unequal fragments and binds stronger to the lighter fragment than to the heavier one. In the interaction studies between the Pt(II) and Pd(II) complexes with DNA, several binding and thermodynamic parameters have been determined, which may provide deeper insights into the mechanism of action of these types of complexes with nucleic acids. (C) 2008 Published by Elsevier Ltd.

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