title: The alkylphospholipid edelfosine shows activity against Strongyloides venezuelensis and induces apoptosis-like cell death.
abstract: 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.
authors.affiliation: Parasite and Molecular Immunology Laboratory, Tropical Disease Research Centre, University of Salamanca (IBSAL-CIETUS), Avda. Licenciado Méndez Nieto s/n, 37007 Salamanca, Spain.
authors.forename: Ana L
authors.initials: AL
authors.lastname: Legarda-Ceballos
authors.affiliation: Parasite and Molecular Immunology Laboratory, Tropical Disease Research Centre, University of Salamanca (IBSAL-CIETUS), Avda. Licenciado Méndez Nieto s/n, 37007 Salamanca, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Rojas-Caraballo
authors.affiliation: Parasite and Molecular Immunology Laboratory, Tropical Disease Research Centre, University of Salamanca (IBSAL-CIETUS), Avda. Licenciado Méndez Nieto s/n, 37007 Salamanca, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: López-Abán
authors.affiliation: Parasite and Molecular Immunology Laboratory, Tropical Disease Research Centre, University of Salamanca (IBSAL-CIETUS), Avda. Licenciado Méndez Nieto s/n, 37007 Salamanca, Spain; Facultad de Ciencias Médicas, Universidad Central del Ecuador-Instituto Nacional de Investigación en Salud Pública (INSPI), Quito, Ecuador.
authors.forename: Ana Lucía
authors.initials: AL
authors.lastname: Ruano
authors.affiliation: Parasite and Molecular Immunology Laboratory, Tropical Disease Research Centre, University of Salamanca (IBSAL-CIETUS), Avda. Licenciado Méndez Nieto s/n, 37007 Salamanca, Spain.
authors.forename: Edward
authors.initials: E
authors.lastname: Yepes
authors.affiliation: Laboratory of Cell Death and Cancer Therapy, Department of Cellular and Molecular Medicine, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), C/Ramiro de Maeztu 9, E-28040 Madrid, Spain.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Gajate
authors.affiliation: Laboratory of Cell Death and Cancer Therapy, Department of Cellular and Molecular Medicine, Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), C/Ramiro de Maeztu 9, E-28040 Madrid, Spain.
authors.forename: Faustino
authors.initials: F
authors.lastname: Mollinedo
authors.affiliation: Parasite and Molecular Immunology Laboratory, Tropical Disease Research Centre, University of Salamanca (IBSAL-CIETUS), Avda. Licenciado Méndez Nieto s/n, 37007 Salamanca, Spain. Electronic address: ama@usal.es.
authors.forename: Antonio
authors.initials: A
authors.lastname: Muro
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007814:Larva / Q000187:drug effects; D051379:Mice; D010742:Phospholipid Ethers / Q000494:pharmacology*; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000494:pharmacology; D013321:Strongyloides / Q000187:drug effects*; D013322:Strongyloidiasis / Q000469:parasitology
chemical_list: D000970:Antineoplastic Agents; D010742:Phospholipid Ethers; D010767:Phosphorylcholine; C026659:edelfosine; C105905:perifosine; C039128:miltefosine
keywords: Alkylphospholipid; Apoptosis; Edelfosine; Strongyloidiasis