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 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 ± 5.4 µM, 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. © 2016 Elsevier B.V.

• Autores: Legarda-Ceballos A.L.; Rojas Caraballo, Jose Vicente; López-Abán J.; Ruano A.L.; Yepes E.; Gajate C.; Mollinedo F.; Muro A.
• Tipo de recurso: Article of journal
• Fecha de publicación: 2016
• Institución: Universidad Cooperativa de Colombia
• Repositorio: Repositorio UCC
• OAI Identifier: oai:repository.ucc.edu.co:20.500.12494/41416
• Acceso en línea: https://doi.org/10.1016/j.dental.2012.09.002; https://www.scopus.com/inward/record.uri?eid=2-s2.0-85062607238&doi=10.1371%2fjournal.pone.0213425&partnerID=40&md5=18df756332a9c86d62ca9bbc4087c4d1; https://hdl.handle.net/20.500.12494/41416
• Palabra clave: edelfosine; ivermectin; miltefosine; perifosine; antineoplastic agent; edelfosine; ether phospholipid; phosphorylcholine; apoptosis; DNA; drug; fragmentation; larva; nematode; parasite; phospholipid; animal cell; animal experiment; animal model; antiprotozoal activity; apoptosis; Article; cell count; DNA fragmentation; drug cytotoxicity; drug efficacy; drug response; drug structure; drug tolerability; endothelium cell; fibroblast; IC50; in vitro study; in vivo study; larva; LD50; liver cell; mouse; nonhuman; Strongyloides venezuelensis; strongyloidiasis; treatment duration; analogs and derivatives; animal; dose response; drug effects; female; parasitology; Strongyloides; strongyloidiasis; Mus; Strongyloides venezuelensis; Animals; Antineoplastic Agents; Apoptosis; Dose-Response Relationship; Drug; Female; Larva; Mice; Phospholipid Ethers; Phosphorylcholine; Strongyloides; Strongyloidiasis
• Rights: closedAccess
• License: http://purl.org/coar/access_right/c_14cb