Hexadecylphosphocholine: oral treatment of visceral leishmaniasis in mice

Abstract

Hexadecylphosphocholine (He-PC), a novel phospholipid derivative, was tested against Leishmania donovani and Leishmania infantum, the causative agents of visceral leishmaniasis. In vitro, promastigotes were highly susceptible to He-PC; the 50% inhibitory concentrations were between 0.89 and 2.25 micrograms/ml for the different leishmanial strains. In vivo, a marked antileishmanial activity in infected BALB/c mice could be demonstrated after oral administration of He-PC. Whereas parasite suppression and killing in the liver were comparable after 5 days of treatment with He-PC (10 or 20 mg/kg of body weight per day administered orally) and sodium stibogluconate (120 mg of pentavalent antimonal agent per kg/day administered subcutaneously), a superior reduction in the parasite load in the spleen and bone marrow was observed after oral treatment with He-PC. After a 4-week treatment period, parasite suppression in the spleen was better than that observed with standard sodium stibogluconate therapy by a factor of more than 600.

Hydrosoluble formazan XTT: its application to natural products drug discovery for Leishmania

“…Antileishmanial activity is expressed as IC 50 , which is a measure of the concentration of test substance that inhibits 50% of parasite growth. The IC 50 values obtained with ketoconazole were 26 ng/ml, 13 Ag/ml for miltefosine and 80 -100 ng/ml for amphotericin B, results which are comparable to published values for these compounds (Berman et al, 1984;Kuhlencord et al., 1992; Golenser et al, 1999, respectively). The results presented above and in Figs.…”

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

“…Portanto, a toxicidade e o índice de recidivas e resistência às drogas justificam a busca de novas drogas para tratar a leishmaniose tegumentar 1 2 4 12 14 15 . A miltefosina (hexadecilfosfocolina), medicamento originalmente desenvolvido como antineoplásico, tem ação eficaz sobre as leishmânias 5 7 8 9 16 18 19 20 22 . Esta droga age interferindo na membrana celular do parasita, sem interagir com o DNA, depois modula a composição lipídica, a permeabilidade e fluidez da membrana, assim como o metabolismo de fosfolipídeos, induzindo morte celular por apoptose 11 22 .…”

Cytotoxic Activities of Alkylphosphocholines against Clinical Isolates of Acanthamoeba spp

“…In addition, they are active against several protozoan parasites such as Leishmania donovani (1,17), Trypanosoma cruzi (23), and Entamoeba histolytica (24). In humans, a clinical study demonstrated that visceral leishman-iasis could be treated successfully by oral treatment with hexadecylphosphocholine (APC1) (10).…”