Synthesis, characterization and in vitro antitumor activity of new palladium(II) complexes with (S,S)-R2edda-type esters

Six palladium(II) complexes with (S,S)-R2edda-type esters ((S,S)-R2edda-type: (S,S)-eddch = (S,S)-ethylenediamine-N,N′-di-2-(3-cyclohexyl)propanoate, R = Me, Et, n-Pr, 1–3; (S,S)-pddch = (S,S)-propylenediamine-N,N′-di-2-(3-cyclohexyl)propanoate, R = Et, n-Pr, 4, 5; and (S,S)-eddip = (S,S)-ethylenediamne-N,N′-di-2-propanoate, R = i-Am, 6) were synthesized, characterized by IR, NMR spectroscopy, ESI-MS and elemental analysis. DFT calculations indicate that in case of 1–4, the most stable isomers are with (S,S)- and (R,S)-configuration of nitrogen atoms, but for complex 6 (R,R)- and (R,S)-N,N′-configured isomers. Furthermore, complex 5 was obtained as (S,S)-N,N′ configured isomer. Cytotoxicity study was performed against human cervical adenocarcinoma (HeLa), human alveolar basal adenocarcinoma (A549) and non-cancerous human fetal lung fibroblast (MRC-5) cell lines using colorimetric MTT assay. From the investigated palladium(II) complexes 2, 3 and 5 exhibited highest cytotoxic potential against HeLa (IC50: 28.5 ± 3.9, 29.5 ± 1.3 and 34.3 ± 3.2, respectively).

Graphical abstractSix new palladium(II) complexes: [PdCl2{(S,S)-R2eddch}], R = Me, Et, n-Pr, 1–3; [PdCl2{(S,S)-R2pddch}], R = Et, n-Pr, 4, 5; [PdCl2{(S,S)-R2eddip}], R = i-Am, 6; were synthesized and characterized. Two diastereoisomers were observed in NMR spectra of 1–4 and 6, but only one for 5. DFT calculations are in agreement with NMR findings. Cytotoxicity of 1–6 was studied on 3 cell lines.Figure optionsDownload full-size imageDownload as PowerPoint slide