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(mu-Cl)(H2O)]2Cl2 (4) were readily synthesized from [Au(PPh3)Cl], RuCl3 x 3 H2O, and CuCl2 x 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 microM (Table 2), which makes these drugs, especially the Cu(II) complex 4, considerably more potent than uncomplexed metronidazole (1; IC50 = 1.81 microM), the current standard drug for the worldwide treatment of amoebiasis.

Crystal structure of hexa-μ-chlorido-μ4-oxido-tetrakis{[1-(2-hydroxyethyl)-2-methyl-5-nitro-1H-imidazole-κN 3]copper(II)} containing short NO2...NO2 contacts

“…medications that are considered to be effective and safe to meet the most important needs in a health system (WHO, 2015). Despite the widespread use of MET as a drug, relatively little structural data concerning its interactions with metal ions exist, and there are few structurally characterized copper compounds of MET (Galvá n-Tejada et al, 2002;Barba-Behrens et al, 1991;Athar et al, 2005;Ratajczak-Sitarz et al, 1998;Bharti et al, 2002). Our recent work has sought to develop further metal-MET chemistry and we have reported structures containing Cu Quinlivan & Upmacis, 2016), as well as Ag and Au (Quinlivan et al, 2015).…”

Crystal structure of bis[1-(2-hydroxyethyl)-2-methyl-5-nitro-1H-imidazole-κN3]silver(I) tetrafluoridoborate methanol monosolvate

“…In addition to coordination to silver, metronidazole has also been shown to coordinate to other metals, and structurally characterized compounds have been reported for Co (Galvá n-Tejada et al, 2002), Cu (Galvá n-Tejada et al, 2002;Barba-Behrens et al, 1991;Athar et al, 2005;Ratajczak-Sitarz et al, 1998;Bharti et al, 2002), Zn (Galvá n-Tejada et al, 2002), Ru (Wu et al, 2003;Kennedy et al, 2006), Rh (Dyson et al, 1990;Nothenberg et al, 1994), Pd (Bharti et al, 2002;De Bondt et al, 1994;Rochon et al, 1993) and Pt (Bharti et al, 2002;Bales et al, 1983). In these compounds, the coordination number of the central atom ranges from four for Cu, Zn, Pd and Pt to six for Ru and Rh.…”

1-Hydroxyethyl-2-methyl-5-nitroimidazolium 3-carboxy-4-hydroxybenzenesulfonate

“…For related literature, see: Athar et al (2005); Bharti et al (2002); Castelli et al (2000); Cohen-Jonathan et al (2001); Crozet et al (2002); Galvá n-Tejada et al (2002); Hodgkiss (1998); Kennedy et al (2006); Meng et al (2007); Skupin et al (1997); Wu et al (2003).…”

“…Recently, many efforts have been devoted to developing some new substitutes for the medicine, i.e. i) metal-organic coordination compounds (Kennedy et al, 2006;Galván-Tejada et al, 2002;Athar et al, 2005;Bharti et al, 2002;Wu et al, 2003), ii) organic substitute derivatives (Crozet et al, 2002, Skupin et al, 1997 and iii) pharmaceutical co-crystals. In this paper, we report the 1:1 molecular adduct formed by metronidazole 5-sulfosalicylic acid (5-H 2 SSA), (I).…”