Anticancer And Antileishmanial In Vitro Activity Of Gold(I) Complexes With 1,3,4-Oxadiazole-2(3h)-Thione Ligands Derived From Delta-D-Gluconolactone

Four gold(I) complexes conceived as anticancer agents were synthesized by reacting [Au(PEt3)Cl] and [Au(PPh3)Cl] with ligands derived from delta-d-gluconolactone. The ligands' structure was designed to combine desired biological properties previously reported for each group. Ligands were synthesized from delta-d-gluconolactone via ketal protection and hydrazide formation followed by cyclization with CS(2)to produce the novel oxadiazolidine-2-thione7and8. Increasing of the ligands' lipophilicity via ketal protection proved useful since all four gold(I) complexes showed anticancer and antileishmanial properties. The IC(50)values are at low micromolar range, varying from 2 to 3 mu mfor the most active compounds. The free D-gluconate 1,3,4 oxadiazole-derived ligands were neither toxic nor presented anticancer or antileishmanial properties. Triethylphosphine-derived compounds9and10were more selective against B16-F10 melanoma cell line. Although similar in vitro antileishmanial activity was observed for the gold(I) precursors themselves and their derived complexes, the latter were three times less toxic for human THP-1 macrophage cell line; this result is attributed to an isomeric variation of the D-gluconate ligand and the oxadiazole portion, which was one of the key concepts behind this work. These findings should encourage further research on gold(I) complexes to develop novel compounds with potential application in cancer and leishmaniasis chemotherapy.