Membrane sterol depletion impairs miltefosine action in wild-type and miltefosine-resistant Leishmania donovani promastigotes
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چکیده
منابع مشابه
Alteration of fatty acid and sterol metabolism in miltefosine-resistant Leishmania donovani promastigotes and consequences for drug-membrane interactions.
Miltefosine (hexadecylphosphocholine [HePC]) is the first orally active drug approved for the treatment of visceral leishmaniasis. In order to investigate the biochemical modifications occurring in HePC-resistant (HePC-R) Leishmania donovani promastigotes, taking into account the lipid nature of HePC, we investigated their fatty acid and sterol metabolisms. We found that the content of unsatura...
متن کاملMiltefosine induces apoptosis-like death in Leishmania donovani promastigotes.
Miltefosine (hexadecylphosphocholine [HePC]) has proved to be a potent oral treatment for human visceral leishmaniasis due to Leishmania donovani. The molecular mechanisms that contribute to the antileishmanial activity of HePC are still unknown. We report that in wild-type promastigotes of Leishmania donovani HePC is able to induce a cell death process with numerous cytoplasmic, nuclear, and m...
متن کاملMiltefosine affects lipid metabolism in Leishmania donovani promastigotes.
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 se...
متن کاملNovel Agents against Miltefosine-Unresponsive Leishmania donovani.
Visceral leishmaniasis is a deadly endemic disease. Unresponsiveness to the only available oral drug miltefosine poses a big challenge for the chemotherapy of the disease. We report a novel molecule, PS-203 {4-(4,4,8-trimethyl-7-oxo-3-oxabicyclo[3.3.1]non-2-yl)-benzoic acid methyl ester}, as effective against a miltefosine-unresponsive strain of the parasite. Further, combinations of PS-203 wit...
متن کاملMiltefosine induces programmed cell death in Leishmania amazonensis promastigotes.
In the current study, we evaluated the mechanism of action of miltefosine, which is the first effective and safe oral treatment for visceral leishmaniasis, in Leishmania amazonensis promastigotes. Miltefosine induced a process of programmed cell death, which was determined by the externalization of phosphatidylserine, the incorporation of propidium iodide, cell-cycle arrest at the sub-G0/G1 pha...
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ژورنال
عنوان ژورنال: Journal of Antimicrobial Chemotherapy
سال: 2009
ISSN: 0305-7453,1460-2091
DOI: 10.1093/jac/dkp321