Stereospecific ligands and their complexes. Part X: Synthesis, characterization and in vitro antitumoral activity of platinum(IV) complexes with O,O '-dialkyl-(S,S)-ethylenediamine-N,N '-di-2-(4-methyl)pentanoate ligands

Abstract

Synthesis of four new platinum(IV) complexes 1-4, with bidentate N,N'-ligand precursors O,O'-dialkyl esters (alkyl = ethyl, n-propyl, n-butyl and n-pentyl), of (S,S)-ethylenediamine-N,N'-di-2-(4-methyl)pentanoic acid dihydrochloride [(S,S)-H(4)eddl]Cl-2 were reported. The composition of the novel platinum complexes was determined by elemental analysis and characterizations were performed by infrared, H-1 and C-13 NMR spectroscopy. DFT calculations indicate formation one (R,R) from three possible diastereoisomers (S,S; R,S). Complexes 1-4 displayed potent anticancer activity. IC50 values range from 0.74 to 70 mu M, against tested cell lines, except for CLL cells. The antitumoral activity of 2-4 was found to be considerably stronger to Jurkat and K562. Cell cycle analysis of cell lines showed G1 arrest in the presence of analyzed complexes.