In vitro anticancer activity of gold(III) complexes with some esters of (S,S)-ethylenediamine-N,N′-di-2-propanoic acid

• Five novel Au(III) complexes with (S,S)-R2eddip esters were prepared.
• [AuCl2{(S,S)-(i-Bu)2eddip}]PF6 forms metal-protein adducts with BSA.
• [AuCl2{(S,S)-(i-Am)2eddip}]PF6 is much more active and selective than cisplatin.
• Complexes induced apoptotic mode of HeLa cell death.

Five novel gold(III) complexes of general formulas [AuCl2{(S,S)-R2eddip}]PF6, ((S,S)-eddip = (S,S)-ethylenediamine-N,N′-di-2-propanoate, R = n-Bu, n-Pe, i-Bu, i-Am, cPe; 1–5, respectively) were synthesized and characterized by UV/Vis, IR and NMR spectroscopy and mass spectrometry. DFT calculations indicated that (R,R)-N,N′-configuration diastereoisomers were the most stable for 1–5. 3 is stable in DMSO for at least 24 h, but immediate hydrolysis in PBS occurs. 3 is readily reduced with ascorbic acid and forms adducts with bovine serum albumin (BSA). In vitro anticancer activity of the gold(III) complexes against human cervix adenocarcinoma HeLa, human myelogenous leukemia K562, human melanoma Fem-x tumor cell lines, as well as against non-cancerous human embryonic lung fibroblast cell line MRC-5 was determined using MTT assay. Complex 4 showed highest activity and selectivity (IC50(Fem-x) = 1.3 ± 0.2; IC50(MRC-5)/IC50(Fem-x) = 72.5 ± 12.4), 4 times more active and 28 times more selective than cisplatin. Complexes induced apoptotic mode of death in a time-dependent manner in HeLa cells.

Synthesis, characterization and biological activity of five novel gold(III) complexes with some R2edda-type esters, [AuCl2{(S,S)-R2eddip}]PF6, R = n-Bu, n-Pe, i-Bu, i-Am, cPe, 1–5, is described. [AuCl2{(S,S)-(i-Bu)2eddip}]PF6 forms metal-protein adducts with BSA. Antitumoral activity was tested in vitro on four tumor cell lines. Complex 4 showed highest activity and selectivity, 4 times more active and 28 times more selective than cisplatin. Apoptosis is the main mode of cell death induced by these compounds in HeLa cells.Figure optionsDownload as PowerPoint slide