Complexes of Pd(II) and Pt(II) with 9-Aminoacridine: Reactions with DNA and Study of Their Antiproliferative Activity

[摘要] Four new metal complexes {M = Pd(II) or Pt(II)} containing the ligand 9-aminoacridine (9AA) were prepared. The compounds were characterized by FT-IR andH1,C13, andP195tNMR spectroscopies. Crystal structure of the palladium complex offormulae[Pd(9AA)(μ-Cl)]2·2DMFwas determined by X-ray diffraction. Two 9-acridine molecules in the imine form bindsymmetrically to the metal ions in a bidentate fashion through the imine nitrogen atom and the C(1)atom of the aminoacridine closing a new five-membered ring. By reaction with phosphine or pyridine,the Cl bridges broke and compounds with general formulae [Pd(9AA)Cl(L)] (whereL=PPh3or py) were formed. A mononuclear complex of platinum of formulae [Pt(9AA)Cl(DMSO)] wasalso obtained by direct reaction of 9-aminoacridine and the complex [PtCl2(DMSO)2]. The capacity of the compounds to modify the secondary and tertiary structures of DNA wasevaluated by means of circular dichroism and electrophoretic mobility. Both palladium and platinumcompounds proved active in the modification of both the secondary and tertiary DNA structures.AFM images showed noticeable modifications of the morphology of the plasmid pBR322 DNA by thecompounds probably due to the intercalation of the complexes between base pairs of the DNA molecule.Finally, the palladium complex was tested for antiproliferative activity against three different humantumor cell lines. The results suggest that the palladium complex of formula[Pd(9AA)(μ-Cl)]2has significant antiproliferative activity, although it is less active than cisplatin.

[学科分类] 物理化学和理论化学