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, [PtCl(4)(R(2)eddp)] (R = Et, 1; n-Pr, 2), containing kappa(2)N,N' bidentate ligands, esters of ethylenediamine-N,N'-di-3-propionic acid (HOOCCH(2)CH(2)NHCH(2)CH(2)NHCH(2)CH(2)COOH, H(2)eddp), are reported. Complexes have been characterized by infrared, (1)H and (13)C NMR spectroscopy and elemental analysis and it was concluded that the coordination of the ligands occurs via nitrogen donor atoms of the ester ligands (R(2)eddp). Cytotoxicity studies were performed for ligand precursors and corresponding platinum(IV) complexes. Although the n-Pr(2)eddp.2HCl itself showed no activity (IC(50) values > 125 microM) 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 (IC(50) = 8.6-49 microM). 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.

Redox activation of metal-based prodrugs as a strategy for drug delivery

“…The cytotoxic activity was correlated with Pt uptake. The compound having R 4 = n -propyl reacted with plasmid DNA as judged by gel electrophoresis studies [47]. …”

Oxidative reactivity and cytotoxic properties of a platinum(II) complex prepared by outer-sphere amide bond coupling

“…The low in vitro cytotoxicities of 1 and 2 measured here suggest that these complexes are poor anticancer drug candidates. In contrast, several of the aforementioned platinum(II) and platinum(IV) complexes with ethylenediamine- N,N ’-diester ligands exhibit IC 50 values of less than 20 μM in several cell lines [49-52, 57, 58]. The reasons for the lower cytoxicities of 1 and 2 relative to these complexes and cisplatin remain to be determined.…”

Synthesis, Characterization, and Cytotoxicity of a Novel Gold(III) Complex with O,O′-Diethyl Ester of Ethylenediamine-N,N′-Di-2-(4-Methyl)Pentanoic Acid

“…0.4 ppm), which also indicated that coordination occurred via nitrogen atoms. In the 13 C NMR spectrum, carbonyl atoms show resonances at expected chemical shifts for this class of compounds where oxygen is not participating in coordination (C 3 , 169 ppm) [33,34]. The resonances of carbon atoms from the ethylenediamine moiety (C 1 ) in the complex is shifted downfield relative to that of the ligand precursor [25].…”