In vivo activity of perifosine against Leishmania amazonensis

M Gabriela Cabrera-Serra1, Basilio Valladares, Jose E Piñero

  • 1University Institute of Tropical Diseases and Public Health of Canary Islands, Laboratory of Chemotherapies against Protozoa, University of La Laguna, Tenerife, Spain.

Acta Tropica
|September 20, 2008
PubMed

Insights

Perifosine, an alkyl-phospholipid, demonstrates higher efficacy than miltefosine in treating experimental cutaneous leishmaniasis caused by Leishmania amazonensis in mice.

Area of Science:

  • Pharmacology
  • Infectious Diseases
  • Drug Discovery

Background:

  • Miltefosine is the primary oral treatment for leishmaniasis.
  • Alkyl-phospholipids like edelfosine and perifosine exhibit in vitro antiparasitic activity against Leishmania species.
  • Perifosine has shown prior in vitro effectiveness against Leishmania amazonensis.

Purpose of the Study:

  • To evaluate the in vivo efficacy of perifosine and edelfosine against cutaneous leishmaniasis.
  • To compare the effectiveness of perifosine with miltefosine in a murine model.

Main Methods:

  • BALB/c mice infected with Leishmania amazonensis were treated orally with edelfosine and perifosine at varying doses and durations.
  • Lesion size, parasitic burden, and parasite viability were assessed to determine treatment efficacy.
  • A comparative study involved treating mice with perifosine (5 mg/kg/day for 14 days) and miltefosine (2.5 mg/kg/day for 28 days).

Main Results:

  • Perifosine exhibited superior activity in the in vivo assay compared to edelfosine.
  • The most effective perifosine treatment scheme (5 mg/kg/day for 14 days) showed higher efficacy than the standard miltefosine treatment (2.5 mg/kg/day for 28 days).

Conclusions:

  • Perifosine demonstrates significant potential as a novel alkyl-phospholipid treatment for cutaneous leishmaniasis caused by Leishmania amazonensis.
  • Further investigation into perifosine as a therapeutic agent for leishmaniasis is warranted.