Synthesis and anti-amoebic activity of gold(I), ruthenium(II), and copper(II) complexes of metronidazole

Abstract

A series of Au, Ru, and Cu complexes of metronidazole (= [1-(2-hydroxyethyl)-2-methyl-5-nitro-1H-imidazole; 1) were prepared as highly potent anti-amoebic drugs. The complexes [Au(PPh3)(1)PF6 (2), [Ru(1)2(Cl)2(H2O)2] (3), and [Cu(1)2(μ-Cl)(H2O)]2Cl2 (4) were readily synthesized from [Au(PPh3)Cl], RuCl3 · 3 H2O, and CuCl2 · 2 H2O, respectively. All complexes were thoroughly characterized by IR, UV/VIS, 1H-NMR, FAB-MS, elemental and thermogravimetric analyses, and, in the case of 4, also by X-ray crystallography (Fig. 1). All complexes were evaluated in vitro as growth inhibitors of Entamoeba histolytica (HM1:IMSS strain). Their IC50 values were in the range of 0.10-0.51 μM (Table 2), which makes these drugs, especially the CuII complex 4, considerably more potent than uncomplexed metronidazole (1; IC50 - 1.81 μM), the current standard drug for the worldwide treatment of amoebiasis. © 2005 Verlag Helvetica Chimica Acta AG, Zürich.