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

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)(mu-Cl)(H2O)](2)Cl-2 (4) were readily synthesized from [Au(PPh3)Cl], RuCl3 center dot 3H(2)O, and CuCl2 center dot 2H(2)O, respectively. All complexes were thoroughly characterized by IR, UV/VIS, H-1-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 mu m (Table 2), which makes these drugs, especially the Cu-11 complex 4, considerably more potent than uncomplexed metronidazole (1: IC50 = 1.81 mu M) the current standard drug for the worldwide treatment of amoebiasis.