Synthesis, characterization, in vitro antitumoral investigations and interaction with plasmid pBR322 DNA of R2eddp-platinum(iv) complexes (R = Et, n-Pr)

Abstract

The studies on synthetic, spectroscopic and biological properties of platinum(IV) complexes, [PtCl₄(R₂eddp)] (R = Et, 1; n-Pr, 2), containing κ²N,N′ bidentate ligands, esters of ethylenediamine-N,N′-di-3-propionic acid (HOOCCH₂CH₂NHCH₂CH₂NHCH₂CH₂COOH, H₂eddp), are reported. Complexes have been characterized by infrared, ¹H and ¹³C NMR spectroscopy and elemental analysis and it was concluded that the coordination of the ligands occurs via nitrogen donor atoms of the ester ligands (R₂eddp). Cytotoxicity studies were performed for ligand precursors and corresponding platinum(IV) complexes. Although the n-Pr₂eddp·2HCl itself showed no activity (IC₅₀ values > 125 μM) in selected cell lines, the activity of complex 2, via apoptotic mode of cell death, has increased significantly for a broad range of cancer cell lines tested in vitro (IC₅₀ = 8.6–49 μM). As it was found that complexes 1 and 2 are able to interact with pBR322 plasmid DNA, platinum(IV) complexes of this type may act as drugs and pro-drugs.