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      Miltefosine affects lipid metabolism in Leishmania donovani promastigotes.

      Antimicrobial Agents and Chemotherapy
      Animals, Antiprotozoal Agents, metabolism, pharmacology, Leishmania donovani, drug effects, genetics, Lipid Metabolism, Parasitic Sensitivity Tests, Phosphorylcholine, analogs & derivatives

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          Abstract

          Miltefosine (hexadecylphosphocholine [HePC]) is the first orally active antileishmanial drug. Transient HePC treatment of Leishmania donovani promastigotes at 10 microM significantly reduced the phosphatidylcholine content and enhanced the phosphatidylethanolamine (PE) content in parasite membranes, suggesting a partial inactivation of PE-N-methyltransferase. Phospholipase D activity did not seem to be affected by HePC. In addition, the enhancement of the lysophosphatidylcholine content could be ascribed to phospholipase A2 activation. Moreover, transient HePC treatment had no effect on the fatty acid alkyl chain length or the fatty acid unsaturation rate. Concerning sterols, we found a strong reduction of the C24 alkylated sterol content, and the enhancement of the cholesterol content could be the result of the HePC condensation effect with sterols. Because some of the effects observed after transient HePC treatment were different from those previously observed in HePC-resistant parasites, it could be hypothesized that continuous in vitro drug pressure induces the mechanisms of regulation in Leishmania lipid metabolism.

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          Author and article information

          Journal
          17242145
          1855451
          10.1128/AAC.01123-06

          Chemistry
          Animals,Antiprotozoal Agents,metabolism,pharmacology,Leishmania donovani,drug effects,genetics,Lipid Metabolism,Parasitic Sensitivity Tests,Phosphorylcholine,analogs & derivatives

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