alexa Effect of the lysophospholipid analogues edelfosine, ilmofosine and miltefosine against Leishmania amazonensis.
Infectious Diseases

Infectious Diseases

Journal of Tropical Diseases & Public Health

Author(s): SantaRita RM, HenriquesPons A, Barbosa HS, de Castro SL

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Abstract OBJECTIVES: Analysis of the effect of edelfosine, ilmofosine and miltefosine on Leishmania amazonensis and of potential targets of these lysophospholipid analogues. METHODS: Quantification and ultrastructural analysis of the effect of lysophospholipid analogues on promastigote forms and on infected peritoneal macrophages, and flow cytometry analysis of treated promastigotes labelled with propidium iodide and rhodamine 123 (Rh123). RESULTS: The lysophospholipid analogues presented potent antiproliferative activity with IC50/3 days of 1.9-3.4 microM for promastigotes and 4.2-9.0 microM for intracellular amastigotes. Treatment with these analogues in Schneider medium for 1 day led to a dose-dependent decrease in Rh123 fluorescence, an effect more accentuated in edelfosine-treated parasites, suggesting interference with the potential of the mitochondrial membrane. In both forms of L. amazonensis, edelfosine induced extensive mitochondrial damage, multinucleation and, in promastigotes, also led to plasma membrane alterations, formation of autophagic structures and membranous arrangements inside the flagellar pocket. CONCLUSIONS: The alkylglycerophosphocholines edelfosine and ilmofosine were more active than the alkylphosphocholine miltefosine against promastigotes and intracellular amastigotes of L. amazonensis, and ultrastructural and flow cytometry data indicate the mitochondrion as a target of edelfosine. This article was published in J Antimicrob Chemother and referenced in Journal of Tropical Diseases & Public Health

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