In Vitro and In Vivo Anti-Schistosomal Activity of the Alkylphospholipid Analog Edelfosine
| Autor: | E. L. Habib Dakir, Julio López-Abán, Antonio Muro, Rubén E. Varela-M, Edward Yepes, Faustino Mollinedo |
|---|---|
| Přispěvatelé: | Sociedad Española de Medicina Tropical y Salud Internacional, Universidad de Salamanca, Junta de Castilla y León, European Commission, Instituto de Salud Carlos III, Red Temática de Investigación Cooperativa en Cáncer (España), Ministerio de Ciencia e Innovación (España) |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Schistosoma Mansoni
lcsh:Medicine ComputingMilieux_LEGALASPECTSOFCOMPUTING Apoptosis Pharmacology chemistry.chemical_compound Mice 0302 clinical medicine Drug Discovery Medicine and Health Sciences lcsh:Science Schistosoma haematobium Mammals 0303 health sciences Multidisciplinary biology Cell Death 3. Good health Praziquantel Cell Processes Vertebrates Schistosoma Schistosoma mansoni medicine.drug Edelfosine Research Article Drug Research and Development 030231 tropical medicine Schistosomiasis Rodents 03 medical and health sciences SDG 3 - Good Health and Well-being Helminths parasitic diseases medicine Animals Drug Discovery for Neglected Diseases 030304 developmental biology Miltefosine lcsh:R Organisms Biology and Life Sciences Cell Biology medicine.disease biology.organism_classification Antiparasitic agent Invertebrates chemistry Immunology lcsh:Q |
| Zdroj: | PLoS ONE Yepes, E, Varela-M, R E, Lopez-Aban, J, Dakir, E L H, Mollinedo, F & Muro, A 2014, ' In Vitro and In Vivo Anti-Schistosomal Activity of the Alkylphospholipid Analog Edelfosine ', PLoS ONE, vol. 9, no. 10, e109431 . https://doi.org/10.1371/journal.pone.0109431 Digital.CSIC. Repositorio Institucional del CSIC instname PLoS ONE, Vol 9, Iss 10, p e109431 (2014) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0109431 |
| Popis: | This is an open-access article distributed under the terms of the Creative Commons Attribution License. [Background]: Schistosomiasis is a parasitic disease caused by trematodes of the genus Schistosoma. Five species of Schistosoma are known to infect humans, out of which S. haematobium is the most prevalent, causing the chronic parasitic disease schistosomiasis that still represents a major problem of public health in many regions of the world and especially in tropical areas, leading to serious manifestations and mortality in developing countries. Since the 1970s, praziquantel (PZQ) is the drug of choice for the treatment of schistosomiasis, but concerns about relying on a single drug to treat millions of people, and the potential appearance of drug resistance, make identification of alternative schistosomiasis chemotherapies a high priority. Alkylphospholipid analogs (APLs), together with their prototypic molecule edelfosine (EDLF), are a family of synthetic antineoplastic compounds that show additional pharmacological actions, including antiparasitic activities against several protozoan parasites. [Methodology/Principal Findings]: We found APLs ranked edelfosine> perifosine> erucylphosphocholine> miltefosine for their in vitro schistosomicidal activity against adult S. mansoni worms. Edelfosine accumulated mainly in the worm tegument, and led to tegumental alterations, membrane permeabilization, motility impairment, blockade of male-female pairing as well as induction of apoptosis-like processes in cells in the close vicinity to the tegument. Edelfosine oral treatment also showed in vivo schistosomicidal activity and decreased significantly the egg burden in the liver, a key event in schistosomiasis. [Conclusions/Significance]: Our data show that edelfosine is the most potent APL in killing S. mansoni adult worms in vitro. Edelfosine schistosomicidal activity seems to depend on its action on the tegumental structure, leading to tegumental damage, membrane permeabilization and apoptosis-like cell death. Oral administration of edelfosine diminished worm and egg burdens in S. mansoni -infected CD1 mice. Here we report that edelfosine showed promising antischistosomal properties in vitro and in vivo. This work was supported by the Spanish Ministerio de Ciencia e Innovación (SAF2011-30518, and RD12/0036/0065 from Red Temática de Investigación Cooperativa en Cáncer, Instituto de Salud Carlos III, cofunded by the Fondo Europeo de Desarrollo Regional of the European Union), European Community's Seventh Framework Programme FP7-2007-2013 (grant HEALTH-F2-2011-256986, PANACREAS), Junta de Castilla y León (CSI052A11-2and SA342U13), Sociedad Española de Medicina Tropical y Salud Internacional (RFEF-SEMTSI 2013) and the Universidad de Salamanca (USAL17008). |
| Databáze: | OpenAIRE |
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