In vivo activity of perifosine against Leishmania amazonensis

Miltefosine has been established as the first oral administration drug against cutaneous and visceral leishmaniasis. Other alkyl-phospholipids such as edelfosine have been tested against Leishmania showing an in vitro antiparasitic activity. Perifosine in vitro activity has been previously demonstrated against different Leishmania species including Leishmania amazonensis. In this study edelfosine and perifosine were orally administered to BALB/c mice at doses of 1 and 2.5 mg/kg/day during 28 days and 5 mg/kg/day during 14 days, starting the treatment 2 weeks after the first treatment scheme. Lesion sizes and parasitic burden as well as viability were determined in order to establish the treatment effectiveness. An assay to compare miltefosine at standard dose of 2.5 mg/kg/day during 28 days to an in vivo treatment with perifosine at the most effective treatment scheme observed in this study 5 mg/kg/day during 14 days, was also developed. Perifosine showed the higher activity in the in vivo assay and is showing as a new possibility within the alkyl-phospholipids group for the treatment against cutaneous leishmaniasis caused by L amazonensis. (C) 2008 Elsevier B.V. All rights reserved.