Diimine Platinum(II) and Palladium(II) Complexes of Dithiocarbamate Derivative as Potential Antitumor Agents: Synthesis, Characterization, Cytotoxicity, and Detail DNA-Binding Studies

Abstract

The synthesis and chemical characterization of two structurally related platinum(II) and palladium(II) complexes, [M(2,2'-bipyridine)(morpholinedithiocarbamate)]NO(3) or [M(bpy)(mor-dtc)]NO(3), where M = Pt(II) or Pd(II), are described. Studies of anti-tumor activities of these complexes against human cell tumor lines (K(562)) have been carried out. They show 50% cytotoxic concentration (Cc(50)) values much lower than that of cisplatin. Both of these water soluble complexes have been shown to interact with calf thymus DNA (ct-DNA) using difference absorption-, fluorescence-, and circular dichroism-titration techniques. These studies showed that both complexes exhibit cooperative binding and presumably intercalate in DNA. These complexes unexpectedly denature DNA at very low concentrations (50-100 microM). Several binding and thermodynamic parameters are also described.