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

Chem Biodivers. 2005 Oct;2(10):1320-30. doi: 10.1002/cbdv.200590104.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amebicides / chemistry
  • Amebicides / pharmacology
  • Animals
  • Copper / chemistry*
  • Copper / pharmacology
  • Entamoeba histolytica / drug effects*
  • Gold / chemistry*
  • Gold / pharmacology
  • Metronidazole / analogs & derivatives*
  • Metronidazole / chemistry
  • Metronidazole / pharmacology*
  • Ruthenium / chemistry*
  • Ruthenium / pharmacology

Substances

  • Amebicides
  • Metronidazole
  • Gold
  • Copper
  • Ruthenium