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)]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.
Athar
Fareeda
F
Department of Chemistry, Jamia Millia Islamia, New Delhi 110025, India.
Husain
Kakul
K
Abid
Mohammad
M
Agarwal
Subhash M
SM
Coles
Simon J
SJ
Hursthouse
Micheal B
MB
Maurya
Mannar R
MR
Azam
Amir
A
D000563:Amebicides / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D003300:Copper / Q000737:chemistry* / Q000494:pharmacology; D004748:Entamoeba histolytica / Q000187:drug effects*; D006046:Gold / Q000737:chemistry* / Q000494:pharmacology; D008795:Metronidazole / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D012428:Ruthenium / Q000737:chemistry* / Q000494:pharmacology
D000563:Amebicides; D008795:Metronidazole; D006046:Gold; D003300:Copper; D012428:Ruthenium