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

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)-H4eddl]Cl2 were reported. The composition of the novel platinum complexes was determined by elemental analysis and characterizations were performed by infrared, 1H and 13C 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 μM, 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.

Novel platinum(IV) complexes containing esters of (S,S)-ethylenediamine-N,N′-di-2-(4-methyl)pentanoic acid were synthesized and tested against MDA-MB-361, MDAMB-453, Jurkat, K562, SW480 and CLL cells. In vitro antitumor activity was accompanied by an important apoptotic fraction of tested cell lines after treatment with complexes 1–4.Figure optionsDownload as PowerPoint slideHighlights
► Synthesized Pt(IV) complexes containing R2edda-type ligands.
► Quantum chemical calculations (DFT level) support experimental findings.
► Complexes 2–4 vs. cisplatin: higher/comparable activity on SW480/Jukart cell line.