Activity of Imidazoles Against Leishmania Tropica in Human Macrophage Cultures

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  • Cell Biology Section, Laboratory of Parasitic Diseases, National Institutes of Health, Department of Parasitology, Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Bethesda, Maryland 20205

The anti-leishmanial activity of four imidazoles has been determined in Leishmania tropica-infected human monocyte-derived macrophage cultures. One of the imidazoles, hydrolyzed ketoconazole [cis-1-{4-[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxyphenyl}piperazine], eliminated 80 and 95% of the parasites at drug concentrations (2.0 and 2.5 µg/ml) that are achievable in vivo by a structurally similar compound, ketoconazole. These results demonstrate that an imidazole has anti-leishmanial activity in a model system, and suggests that hydrolyzed ketoconazole should be considered for in vivo trials in animal models of the disease.