Palladium(II) complexes with R2edda derived ligands. Part IV. O,O′-dialkyl esters of (S,S)-ethylenediamine-N,N′-di-2-(4-methyl)-pentanoic acid dihydrochloride and their palladium(II) complexes: Synthesis, characterization and in vitro antitumoral activity

Four novel bidentate N,N′-ligand precursors, including O,O′-dialkyl esters (alkyl = ethyl, n-propyl, n-butyl and n-pentyl), L1·2HCl–L4·2HCl, of (S,S)-ethylenediamine-N,N′-di-2-(4-methyl)-pentanoic acid dihydrochloride [(S,S)-H4eddl]Cl2 and the corresponding palladium(II) complexes 1–4, were prepared and characterized by IR, 1H NMR and 13C NMR spectroscopy and elemental analysis. In vitro cytotoxicity of all compounds was determined against chronic lymphocytic leukemia cells (CLL). The compounds were found to exhibit higher antitumoral activity than cisplatin. The most active compound 2, [PdCl2{(S,S)-nPr2eddl}], was found to be 13.6 times more active than cisplatin on CLL cells.

Graphical abstractCompounds R2edda·2HCl-type esters (L1·2HCl–L4·2HCl) and corresponding palladium(II) complexes (1–4) were synthesized, characterized and tested in vitro against chronic lymphocytic leukemia cells. Cytotoxicity depends on ester R substituents in both esters (IC50: nPe < nBu ≈ nPr < Et) and palladium(II) complexes (IC50: nPr < nPe < nBu ≈ Et). The most active compound 2, [PdCl2{(S,S)-nPr2eddl}], was found to be 13.6 times more active than cisplatin on CLL cells.Figure optionsDownload full-size imageDownload as PowerPoint slide