Synthesis, crystal structure, and enhancement of the efficacy of metronidazole against Entamoeba histolytica by complexation with palladium(II), platinum(II), or copper(II)

Bharti, Neelam, Coles, Simon J., Hursthouse, Michael B., Mayer, Thomas A., Gonzalez Garza, M.T., Cruz-Vega, Delia E., Mata-Cardenas, Benito D., Naqvi, Fehmida, Maurya, Mannar R. and Azam, Amir (2002) Synthesis, crystal structure, and enhancement of the efficacy of metronidazole against Entamoeba histolytica by complexation with palladium(II), platinum(II), or copper(II). Helvetica Chimica Acta, 85 (9), 2704-2712. (doi:10.1002/1522-2675(200209)85:9<2704::AID-HLCA2704>3.0.CO;2-X).

Abstract

Reaction of trans-[PdCl2(DMSO)(2)]. cis-[PtCl2(DMSO)(2)]. and [Cu(OAc)(2)](H2O)-H-. with metronidazole (mnz) leads to the formation of new complexes, i.e., trans-[PdCl2(mnz)(2)] (1), trans-[PtCl2(mnz)(2)] (2). and trans-[Cu-2(OAc)(4)(mnz)(2)] (3), respectively. Complexes 1-3 crystallize all in the centrosymmetric monoclinic space group P2(1)/c with Z = 8. Unit-cell parameters for these complexes are: 1, a = 7.1328(14) Angstrom, b = 20.699(4) Angstrom, c = 7.1455(14) Angstrom, and beta = 116.17(3)degrees; 2, a = 9.9169(14) Angstrom, b = 21.853(4) Angstrom, c = 6.7218(13) Angstrom, and beta = 110.79(3)degrees: 3. a = 9.1663(18) Angstrom, b = 19.129(4) Angstrom, c = 8.9446(18) Angstrom, and beta = 116.44(3)degrees. The complexes 1 and 2 maintain an ideal square-planar geometry. In complex 3, the H2O molecules of the starting complex are replaced by metronidazole while maintaining a dimeric structure of [Cu(OAc)(2)]. Each Cu ion has an ideal octahedral structure, though distortion occurs in the equatorial position where the acetato ligands are attached. The Cu-Cu separation of 2.6343(8) Angstrom indicates considerable metal-metal interaction. The testing of the antiamoebic activity of these complexes against the protozoan parasite Entamoeba histolytica suggests that compound 1-3 might be endowed with important antiamoebic properties since they showed IC50 values in a muM range better than metronidazole (Table 2). Thus, compound 1 displayed more effective amoebicidal activity than metronidazole (IC50 values of 0.103 muM vs. 1.50 muM resp.).

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Contributors

Author: Simon J. Coles

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