DNA modification by cisplatin-like Pt(II) complexes containing 1,1′-binaphtyl-2,2′-diamine ligand does not correlate with their antiproliferative activity in cancer cells.

Abstract

DNA-reactive platinum complexes, such as cisplatin and its antitumor derivatives, are presupposed to kill actively proliferating cancer cells. Thus, the intense research of the mechanism of action (MoA) of this class of platinum drugs led to the conclusion that a major factor responsible for antitumor effects of conventional platinum drugs and their derivatives is DNA damage induced by their coordinative binding. Here, we present the results of the investigations aimed at clarification of the DNA binding modes of two direct derivatives of cisplatin, such as enantiomeric Pt(II) complexes, R- and S-1,1′-binaphthyl-2,2′-diaminodichlorido-Pt(II) complexes (R- and S-[Pt(DABN)Cl2]), and compared these modes to that of cisplatin. We show that the chirality of [Pt(DABN)Cl2] complexes can markedly affect their DNA binding mode. On the other hand, the variations in DNA binding do not translate directly into cellular processing and toxicity in cancer cells. Thus, the results are consistent with the view and support the hypothesis that, in contrast to conventional platinum drugs and their derivatives, the DNA damage resulting from the binding of the [Pt(DABN)Cl2] complexes is not a major factor accountable for their biological actions.