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Activity of Imidazoles Against Leishmania Tropica in Human Macrophage Cultures
Jonathan Dembitz Berman
Jonathan Dembitz Berman
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
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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.
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