Solution study under physiological conditions and cytotoxic activity of the gold(III) complexes with L-histidine-containing peptides

Abstract

Proton NMR spectroscopy and cyclic voltammetry have been applied to study the stability of three gold(III) complexes with L-histidine-containing peptides, [Au(Gly-L-His-N,N?,N??)Cl]NO3.1.25H2O (Au1), [Au(L-Ala-L-His-N,N?,N??)Cl]NO3.2.5H2O (Au2) and [Au(Gly-Gly-L-His-N,N?,N??,N???)]Cl.H2O (Au3) under physiologically relevant conditions. It was found that tridentate coordination of Gly-L-His and L-Ala-L-His dipeptides, as well as tetradentate coordination of Gly-Gly-L-His tripeptide in Au1, Au2 and Au3 complexes, respectively, stabilized +3 oxidation state of gold and prevented its reduction to Au(I) and Au(0). No release of the coordinated peptides from Au(III) was observed under these experimental conditions. Considering remarkable stability of Au1, Au2 and Au3 complexes, their cytotoxic activity was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay toward five human tumor cell lines, MCF-7 (human breast adenocarcinoma), HT-29 (human colon adenocarcinoma), HeLa (human cervix carcinoma), HL-60 (human promyelocytic leukemia), Raji (human Burkitt?s lymphoma) and one human normal cell line MRC-5 (human fetal lung fibroblasts). While the cytotoxic activity of Au1, Au2 and Au3 against investigated human malignant cell lines was strongly cell line dependent, none of these complexes was cytotoxic against normal MRC-5 cell line. This study can contribute to the future development of gold(III)-peptide complexes as potential antitumor agents.