Mixed complexes of Pt(II) and Pd(II) with ethylsarcosinedithiocarbamate and 2-/3-picoline as antitumor agents

J Inorg Biochem. 2005 Nov;99(11):2139-50. doi: 10.1016/j.jinorgbio.2005.07.016. Epub 2005 Sep 13.

Abstract

The [M(ESDT)Cl](n) (M=Pt(II), Pd(II); ESDT=EtO(O)CCH(2)N(CH(3))CS(2)(-), ethylsarcosinedithiocarbamate ion) species have been reacted with 2- or 3-picoline in dichloromethane in order to obtain mixed ligand complexes of the type [M(ESDT)(L)Cl] (L=2-picoline, 3-picoline). The synthesized compounds have been isolated, purified and characterized by means of elemental analyses, (1)H-/(13)C-/(1)H(13)C-HMBC (heteronuclear multiple bonding coherence) NMR and FT-IR spectroscopy. The biological activity of the compounds reported here has been then determined in terms of cell growth inhibition, DNA synthesis inhibition, detection of interstrand cross-links and DNA-protein cross-links, and micronuclei (MN) detection on a panel of tumor cell lines both sensitive and resistant to cisplatin. On the basis of the experimental results, coordination in the above mentioned complexes takes place in a near square-planar geometry, the dithiocarbamate moiety acting as a chelating agent, whereas the two remaining coordination sites are occupied by a chlorine atom and an amino ligand. Above all, [Pt(ESDT)(2-picoline)Cl] complex has shown very encouraging cytotoxicity levels higher or, at least, comparable to those exerted by cisplatin in the same experimental conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cells, Cultured
  • HL-60 Cells
  • HeLa Cells
  • Humans
  • In Vitro Techniques
  • Palladium / chemistry
  • Palladium / pharmacology*
  • Picolines / chemistry
  • Picolines / pharmacology*
  • Platinum / chemistry
  • Platinum / pharmacology*
  • Sarcosine / analogs & derivatives*
  • Sarcosine / chemistry
  • Sarcosine / pharmacology
  • Spectroscopy, Fourier Transform Infrared
  • Thiocarbamates / chemistry
  • Thiocarbamates / pharmacology*

Substances

  • Antineoplastic Agents
  • Picolines
  • Thiocarbamates
  • sarcosine dithiocarbamate
  • Platinum
  • Palladium
  • Sarcosine