Synthesis and characterization of palladium(II) and platinum(II) complexes with Schiff bases derivatives of 2-pyridincarboxyaldehyde. Study of their interaction with DNA

• Published in: Journal of inorganic biochemistry Vol. 100; no. 8; pp. 1368 - 1377
• Main Authors: García-Friaza, Gloria, Fernández-Botello, Alfonso, Pérez, Jose M., Prieto, Maria J., Moreno, Virtudes
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2006
• Subjects: AFM imaging; Aldehydes - chemistry; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cisplatin - pharmacology; DNA - chemistry; DNA - drug effects; DNA - metabolism; DNA Adducts - ultrastructure; Female; Humans; Inhibitory Concentration 50; Mass Spectrometry; Microscopy, Atomic Force; Molecular Structure; Organic Chemicals - chemistry; Organic Chemicals - metabolism; Ovarian Neoplasms - drug therapy; Palladium - chemistry; Palladium - metabolism; Palladium complexes; Platinum - chemistry; Platinum - metabolism; Platinum antitumor complexes; Pyridines - chemistry; Schiff bases; Schiff Bases - chemistry; Schiff Bases - metabolism; Schiff bases; Platinum antitumor complexes; AFM imaging; Palladium complexes
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2006.03.011

Several Schiff bases ligand derivatives of 2-pyridincarboxyaldehyde and different amines, together with their palladium(II) and platinum(II) complexes have been synthesised and characterised. The aim of this study is to probe the influence of substituents beared on the pyridyl/toluine ring at different position to their possible antitumor activity. The amines used were o-, m-, p-toluidine and 4-hydroxyaniline. All the compounds were characterised by elemental analysis, FT-IR spectroscopy, 1H and 195Pt NMR spectroscopy and matrix assisted laser desorption/ionization time-of-flight mass spectroscopy. The formation of DNA adducts were analysed by circular dichroism and electrophoretic mobility. Atomic force microscopy images of the compounds with plasmid DNA pBR322 were also obtained. In all cases changes in the second and tertiary structure of DNA could be observed as a consequence of the covalent interaction of the palladium(II) or platinum(II) ions with the N of the nucleobases. However, there are not significant differences in the behavior of the complexes related to the position of the methyl groups or the presence of the OH group. Values of IC 50 were also calculated for the platinum(II) complexes for several pairs of ovarian tumor cell lines which were either sensitive or resistant to cisplatin. Finally in vitro apoptosis studies for platinum(II) complexes with ovarian tumor cell lines A2780/A2780cisR were carried out. The results indicated interesting antiproliferative activity and significant apoptosis induction.