Study of the synthesis, antiproliferative properties, and interaction with DNA and polynucleotides of cisplatin-like Pt(II) complexes containing carcinogenic polyaromatic amines

J Biol Inorg Chem. 2013 Oct;18(7):791-801. doi: 10.1007/s00775-013-1022-4. Epub 2013 Jul 20.

Abstract

The chemical and biological features of two newly synthesized [PtCl2(L)(2-aminonaphthalene)] complexes (L is NH3 or 2-aminonaphthalene) were compared with those of two already reported enantiomeric complexes of formula [PtCl2(DABN)] [DABN is (R)-1,1'-binaphthyl-2,2'-diamine or (S)-1,1'-binaphthyl-2,2'-diamine]. Solution behavior, lipophilicity, cytotoxicity with regard to one colorectal (HCT116) and two ovarian (A2780 and A2780Cp8) human carcinoma cell lines, and in vitro DNA- and G-quadruplex-binding properties were evaluated. In particular, the cytotoxicity of [PtCl2(NH3)(2-aminonaphthalene)] was better than that of cisplatin for all cell lines, and rather resembled that of oxaliplatin. The solution behavior of the whole series of complexes and the absence of an evident relationship between lipophilicity and cytotoxicity seem to suggest that all these experimental parameters are probably smoothed out during the 3-day cytotoxicity experiments and do not strongly affect the half-maximal inhibitory concentrations. The results of electrophoretic studies indicate that different kinds of interaction with DNA can be involved in the mode of action of these complexes, with intercalation in double-stranded DNA and stacking on G-quadruplex DNA being strongly implicated in particular for [PtCl2(NH3)(2-aminonaphthalene)].

MeSH terms

  • Amines / chemistry*
  • Carcinogens / chemistry*
  • Cell Proliferation / drug effects
  • Chemistry Techniques, Synthetic
  • Cisplatin / analogs & derivatives*
  • DNA, Superhelical / metabolism*
  • HCT116 Cells
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Organoplatinum Compounds / chemical synthesis
  • Organoplatinum Compounds / chemistry
  • Organoplatinum Compounds / metabolism*
  • Organoplatinum Compounds / pharmacology*
  • Polynucleotides / metabolism*
  • Solutions

Substances

  • Amines
  • Carcinogens
  • DNA, Superhelical
  • Organoplatinum Compounds
  • Polynucleotides
  • Solutions
  • Cisplatin