Leishmanicidal Activity of Edelfosine, Miltefosine and Ilmofosine

Abstract

Abstract:The anti-proliferative action of three alkyl-lysophospholipid derivatives, edelfosine (ET-OCH), miltefosine (Hexadecylphosphocholine), and ilmofosine (BM 14.440) has been studied on the promastigotes and amastigotes of Leishmania donovani. The effect of the three drugs has previously been studied, but the action mode was not clearly elucidated. In this study the effect on the intracellular amastigote forms was evaluated by two different methods: the traditional method, counting the amastigotes within the macrophages stained with Giemsa; and by a new method, staining the nuclear macrophages and amastigotes with ethidium bromide and counting the different population by flow cytometry. This new method, based on the flow cytometry, shows an advantage for evaluating the anti-proliferative effects in intracellular parasites. The ED50 were calculated for the drug activity after 72 hr, and for the three alkyl-lysophospholipid derivatives it were in the range of 26.73-33.31 mM against promastigotes and in the range of 16.46-23.16 against amastigotes. Also, studying the effect against macrophages J774A1, the ED50 were in the range of 24.28-26.38 mM. The effect of the alkyl-lysophospholipids in the macromolecular biosynthesis of the Leishmania donovani, was studied comparing the incorporation of labelled analogues ([

Treatment Failure and Miltefosine Susceptibility in Dermal Leishmaniasis Caused by Leishmania Subgenus Viannia Species

“…A detailed comparative study using a single strain of L. donovani suggested that promastigotes and intracellular amastigotes within peritoneal mouse macrophages were comparably susceptible to miltefosine, with a trend toward greater susceptibility of intracellular amastigotes (27). The greater susceptibility of amastigotes may be attributable to increased cytotoxicity within the macrophage, conferred by alkyl-lysophospholipids promoting the death of intracellular parasites either by direct action of the drug or as a secondary effect on host cells as oxidative burst or production of reactive-oxygen metabolites (28). In contrast to other stud- ies, our study included miltefosine-susceptible and -resistant controls that provided internal references for the interpretation of effective concentrations and reduction of parasite burden.…”

Miltefosine induces programmed cell death in Leishmania amazonensis promastigotes

“…Other alkylphospholipids such as edelfosine, ilmofosine and perifosine have been shown to display antiparasitic activity against Leishmania spp in vitro (Escobar et al 2002, Azzouz et al 2005. Perifosine and miltefosine exhibited a similar activity against L. amazonensis in vitro, whereas edelfosine showed the lowest activity.…”

In a trial of the use of miltefosine to treat HIV‐related cryptosporidiosis in Zambian adults, extreme metabolic disturbances contribute to high mortality

“…obs.). As these data indicate that miltefosine is as effective, in vitro, against C. parvum as against Leishmania donovani (Azzouz et al, 2005), it was hoped that the drug would have similar in-vivo efficacy against the two species of parasite.…”