The alkylphospholipid edelfosine shows activity against Strongyloides venezuelensis and induces apoptosis-like cell death

Strongyloidiasis is widely distributed in the tropical and subtropical areas. Ivermectin is the drug of choice for the treatment. However, the concerns about relying treatment on a single drug make identification of new molecules a priority. Alkylphospholipid analogues, including edelfosine, are a g...

Full description

Autores:
Ceballos Legarda, Ana Lucya
Rojas Caraballo, José Vicente
López Aban, Julio
Ruano, Ana Lucia
Yepes Victoria, Edward
Gajate, Consuelo
Mollinedo, Faustino
Muro, Antonio
Tipo de recurso:
Article of journal
Fecha de publicación:
2016
Institución:
Universidad Cooperativa de Colombia
Repositorio:
Repositorio UCC
Idioma:
OAI Identifier:
oai:repository.ucc.edu.co:20.500.12494/1002
Acceso en línea:
https://hdl.handle.net/20.500.12494/1002
Palabra clave:
Strongyloidiasis
Alkylphospholipid
Edelfosine
Apoptosis
Rights
openAccess
License
Licencia CC
Description
Summary:Strongyloidiasis is widely distributed in the tropical and subtropical areas. Ivermectin is the drug of choice for the treatment. However, the concerns about relying treatment on a single drug make identification of new molecules a priority. Alkylphospholipid analogues, including edelfosine, are a group of synthetic compounds that have shown activity against some parasites. The objective was to assess the in vitro and in vivo activity of edelfosine, miltefosine, perifosine against Strongyloides venezuelensis. Moreover, apoptosis-like mechanism in larvae after treatment was studied. Edelfosine displayed the highest activity and the best selectivity index (LD50=49.6 ± 5.4μM, SI=1.1) compared to miltefosine or perifosine. Third stage larvae after culture with edelfosine were not able to develop an infection in mice. Treatment of mice with edelfosine showed reduction of 47% in parasitic females allocated in the gut. Moreover, DNA fragmentation was observed by TUNEL staining in larvae treated with edelfosine. These results suggest that edelfosine could be an effective drug against strongyloidiasis, probably through induction of apoptosis-like cell death.