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

Abstract

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 and 1H, 13C, and 195Pt NMR spectroscopies. Crystal structure of the palladium complex of formulae [Pd(9AA)(μ-Cl)]2 · 2DMF was determined by X-ray diffraction. Two 9-acridine molecules in the imine form bind symmetrically 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)] (where L = PPh3 or py) were formed. A mononuclear complex of platinum of formulae [Pt(9AA)Cl(DMSO)] was also obtained by direct reaction of 9-aminoacridine and the complex [PtCl2(DMSO2]. The capacity of the compounds to modify the secondary and tertiary structures of DNA was evaluated by means of circular dichroism and electrophoretic mobility. Both palladium and platinum compounds 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 the compounds 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 human tumor cell lines. The results suggest that the palladium complex of formula [Pd(9AA)(μ-Cl)]2 has significant antiproliferative activity, although it is less active than cisplatin.

DNA interaction and cytotoxicity studies of new ruthenium(II) cyclopentadienyl derivative complexes containing heteroaromatic ligands

“…3(a) and (b) respectively. In the image (b), several supercoiled forms of plasmid DNA strongly modified, could indicate interaction with DNA in a similar way than that previously observed for typical intercalating molecules like 9-aminoacridine [30,31]. The study of the variation of the viscosity of a Calf Thymus DNA solution incubated with the compound at different relationships compound/DNA shows an increasing on the viscosity which is observed when intercalation occurs.…”

Inhibition of cancer cell growth by ruthenium(II) cyclopentadienyl derivative complexes with heteroaromatic ligands

“…Intercalation of aromatic rings between base pair of DNA is the most probable way of interaction. The image obtained is similar to others obtained for intercalators [41,42]. On the contrary, in complex 2, there are two monodentate phosphines and, at least one of them, SO 3 ], 2, produced a decrease of cell survival of more than 90% at 500 nM in both cells lines (Fig.…”

Synthesis, structural characterization and DNA binding affinity of new bioactive nano‐sized transition metal complexes with sulfathiazole azo dye for therapeutic applications

“…It is apparent that most inspected materials displayed an inhibition of cell viability and increased cytotoxic influence towards MCF‐7 according to the following order: H 2 L < complex 4 < complex 2 < complex 5 < complex 3 < complex 1 . These results indicate that the type of metal ions and the nature of the ligand are the key factors affecting the anticancer efficiency of the metallic compounds . The Cu(II) complex exhibited IC 50 of 3.47 μg ml −1 (5.53 μM), greater than that of the well‐known standard drug cisplatin (IC 50 = 3.67 μg ml −1 (12.23 μM)), towards HepG‐2 cells.…”