Gold(III) complexes with esters of cyclohexyl-functionalized ethylenediamine-N,N′-diacetate

• Six novel Au(III) complexes with R2eddch esters were synthesized.
• [AuCl2{(S,S)-(i-Am)2eddch}] PF6 is more active against K562 cells than cisplatin.
• The mode of HeLa cell death induced by five complexes is apoptosis.
• Au(III) complexes inhibit cell entry in mitosis of K562 cells.

Six novel gold(III) complexes containing O,O′-dialkyl-(S,S)-ethylenediamine-N,N′-di-2-(3-cyclohexyl)propanoate ([AuCl2{(S,S)-R2eddch}]PF6, R = Me, Et, n-Pr, n-Bu, i-Bu, i-Am; 1–6, respectively) were synthesized and characterized by elemental analysis, UV/Visible, IR and NMR spectroscopy, mass spectrometry and differential pulse voltammetry. Density functional theory (DFT) calculations confirmed that diastereoisomer with the N,N′ atoms configured (S,S) was the most stable. In vitro antiproliferative activity was determined against human cervix adenocarcinoma HeLa and human myelogenous leukemia K562 tumor cell lines, as well as against rested and stimulated normal immunocompetent human peripheral blood mononuclear cells (PBMC) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Complex 6 expressed the highest activity against K562 cells (IC50 = 3.8 ± 0.5 μM). Apoptosis, seen as condensation of HeLa cell nuclei was the mode of cell death induced by complexes 2–6. Complexes 3–6 induced death of K562 cells inhibiting cell entry in mitosis.

Biological potential of gold(III) complexes with cyclohexyl-functionalized R2edda-type esters is described. Compounds induced apoptotic mode of cell death.Figure optionsDownload as PowerPoint slide