Trypanocidal activity of [Au(terpy)Cl]Cl2

Gold complexes are used in rheumatoid arthritis therapy since the begging of the past century. Auranofin and the other gold metallopharmaceuticals are Au(I) complexes, but the biological activity of Au(III) is not unexplored. Gold(III) and Pt(II) are isoelectronic and their complexes are promising antitumor agents1, which driven researchers to pursue this path. Anticancer compounds often present trypanocidal activity2, and this was the reason for choosing [Au(terpy)Cl]Cl2 and evaluate its trypanocidal activity.
2,2’,2’’-Terpyridine was purchased from Sigma-Aldrich, [Au(terpy)Cl]Cl2 was synthesized as described elsewhere3. In vitro cytotoxicity assay was performed through MTT method, using LLC-MK2 (Macaca mulatta kidney epithelial cells), in the same experimental conditions adopted to in vitro trypanocidal activity, as described next. LLC-MK2 cells (5104 cells/well) were plated at 96-well plate with Trypanosoma cruzi trypomatigotes forms (1:10 cells:parasites) of Tulahuen-LacZ strain. After 48 h, the infected cells were washed with PBS and fresh medium was added with compounds (2-0.018 μM) and benznidazole (100-0.78 μM), which were incubated during 72 h. After this time, the viability of T.cruzi amastigotes forms was measured by CPRG method. We observed strong trypanocidal activity of both terpyridine and [Au(terpy)Cl]Cl2, more the 20 times greater than benznidazole, the reference drug. Although somewhat cytotoxic, both compounds present Selectivity Index higher than 10, the minimum stablished by WHO4. Figure 1 and table 1 summarizes these results.