The activity of alkyl phosphorylcholines and related derivatives against Leishmania donovani

Croft, Simon L.; Neal, R. A.; Pendergast, William; Chan, Jason S.

doi:10.1016/0006-2952(87)90543-0

Cited by 189 publications

(120 citation statements)

References 11 publications

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“…3B) when infected cells were treated with CpG alone (1 or 5 M; 24 to 72 h). As expected, miltefosine-induced parasite killing was effective under all conditions (50,51).…”

Section: Resultssupporting

confidence: 84%

Local Delivery of the Toll-Like Receptor 9 Ligand CpG Downregulates Host Immune and Inflammatory Responses, Ameliorating Established Leishmania (Viannia) panamensis Chronic Infection

et al. 2017

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Infection by Leishmania (Viannia) panamensis, the predominant etiologic agent for cutaneous leishmaniasis in Colombia, is characterized by a chronic mixed inflammatory response. Current treatment options are plagued by toxicity, lengthy treatment regimens, and growing evidence of drug resistance. Immunotherapy, modulating the immune system to mount a protective response, may provide an alternate therapeutic approach. We investigated the ability of the Toll-like receptor 9 (TLR9) ligand CpG to modulate established disease in the L.

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“…3B) when infected cells were treated with CpG alone (1 or 5 M; 24 to 72 h). As expected, miltefosine-induced parasite killing was effective under all conditions (50,51).…”

Section: Resultssupporting

confidence: 84%

Local Delivery of the Toll-Like Receptor 9 Ligand CpG Downregulates Host Immune and Inflammatory Responses, Ameliorating Established Leishmania (Viannia) panamensis Chronic Infection

et al. 2017

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“…Tem sido testada com bons resultados in vitro, em formas promastigotas e amastigotas de Leishmania donovani, desde 1987 3 Tendo em vista a importância das leishmanioses e as dificuldades envolvidas em seus tratamentos, tais como resistência aos antimoniais, a miltefosina surgiu como um medicamento promissor para o tratamento da leishmaniose tegumentar, sendo administrado por via oral e com menos efeitos colaterais, chegando a ser registrado na Índia para o tratamento da leishmaniose visceral (calazar) em 2002 21 .…”

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Estudo comparativo entre miltefosina oral e antimoniato de N-metil glucamina parenteral no tratamento da leishmaniose experimental causada por Leishmania (Leishmania) amazonensis

Filho

Lucas

Sampaio

2008

Rev. Soc. Bras. Med. Trop.

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Vinte e cinco camundongos infectados com Leishmania amazonensis foram tratados com antimoniato de N-metil glucamina e miltefosina oral. Critérios: medidas das patas, pesquisa de amastigotas e culturas após-tratamento. Miltefosina: 2,43mm e glucamina 3,46mm (p=0,05). Miltefosina: esfregaços e culturas negativos. Glucamina: 2 esfregaços positivos e culturas positivas (p<0,05). Concluímos que miltefosina foi semelhante à glucamina.

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“…The quest for new drugs led to amphotericin B and paromomycin (4), both not orally bioavailable. By contrast, because of its oral bioavailability, miltefosine became the drug of choice for treating VL patients (27).…”

Section: Discussionmentioning

confidence: 99%

Platelet-Activating Factor Receptor Contributes to Antileishmanial Function of Miltefosine

Gangalum

Castro

Vieira

et al. 2015

The Journal of Immunology

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Miltefosine [hexadecylphosphocholine (HPC)] is the only orally bioavailable drug for the disease visceral leishmaniasis, which is caused by the protozoan parasite Leishmania donovani. Although miltefosine has direct leishmanicidal effects, evidence is mounting for its immune system–dependent effects. The mechanism of such indirect antileishmanial effects of miltefosine remains to be discovered. As platelet-activating factor and HPC share structural semblances and both induce killing of intracellular Leishmania, we surmised that platelet-activating factor (PAF) receptor had a significant role in the antileishmanial function of miltefosine. The proposition was supported by molecular dynamic simulation of HPC docking into PAF receptor and by comparison of its leishmanicidal function on PAF receptor–deficient macrophages and mice under HPC treatment. We observed that compared with wild-type macrophages, the PAF receptor–deficient macrophages showed 1) reduced binding of a fluorescent analog of HPC, 2) decreased TNF-α production, and 3) lower miltefosine-induced killing of L. donovani. Miltefosine exhibited significantly compromised leishmanicidal function in PAF receptor–deficient mice. An anti-PAF receptor Ab led to a significant decrease in miltefosine-induced intracellular Leishmania killing and IFN-γ production in a macrophage–T cell coculture system. These results indicate significant roles for PAF receptor in the leishmanicidal activity of HPC. The findings open new avenues for a more rational understanding of the mechanism of action of this drug as well as for improved therapeutic strategies.

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The activity of alkyl phosphorylcholines and related derivatives against Leishmania donovani

Cited by 189 publications

References 11 publications

Local Delivery of the Toll-Like Receptor 9 Ligand CpG Downregulates Host Immune and Inflammatory Responses, Ameliorating Established Leishmania (Viannia) panamensis Chronic Infection

Local Delivery of the Toll-Like Receptor 9 Ligand CpG Downregulates Host Immune and Inflammatory Responses, Ameliorating Established Leishmania (Viannia) panamensis Chronic Infection

Estudo comparativo entre miltefosina oral e antimoniato de N-metil glucamina parenteral no tratamento da leishmaniose experimental causada por Leishmania (Leishmania) amazonensis

Platelet-Activating Factor Receptor Contributes to Antileishmanial Function of Miltefosine

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