Possible Mechanism of Miltefosine-Mediated Death of Leishmania donovani
نویسندگان
چکیده
منابع مشابه
Possible mechanism of miltefosine-mediated death of Leishmania donovani.
Miltefosine causes leishmanial death, but the possible mechanism(s) of action is not known. The mode of action of miltefosine was investigated in vitro in Leishmania donovani promastigotes as well as in extra- and intracellular amastigotes. Here, we demonstrate that miltefosine induces apoptosis-like death in L. donovani based on observed phenomena such as nuclear DNA condensation, DNA fragment...
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...
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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 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 کاملGenomic Appraisal of the Multifactorial Basis for In Vitro Acquisition of Miltefosine Resistance in Leishmania donovani.
Protozoan parasites of the Leishmania donovani complex are the causative agents of visceral leishmaniasis (VL), the most severe form of leishmaniasis, with high rates of mortality if left untreated. Leishmania parasites are transmitted to humans through the bite of infected female sandflies (Diptera: Phlebotominae), and approximately 500,000 new cases of VL are reported each year. In the absenc...
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ژورنال
عنوان ژورنال: Antimicrobial Agents and Chemotherapy
سال: 2004
ISSN: 0066-4804,1098-6596
DOI: 10.1128/aac.48.8.3010-3015.2004