English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/112373
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

DC FieldValueLanguage
dc.contributor.authorSánchez-Fernández, Elena M.-
dc.contributor.authorGómez-Pérez, Veronica-
dc.contributor.authorGarcía-Hernández, Raquel-
dc.contributor.authorGarcía-Fernández, José Manuel-
dc.contributor.authorPlata, Gabriela B.-
dc.contributor.authorPadrón, José M.-
dc.contributor.authorOrtiz-Mellet, Carmen-
dc.contributor.authorCatanys, Santiago-
dc.contributor.authorGamarro, Francisco-
dc.date.accessioned2015-03-16T08:30:51Z-
dc.date.available2015-03-16T08:30:51Z-
dc.date.issued2015-
dc.identifier.citationRSC Advances, 5: 21812 (2015)es_ES
dc.identifier.urihttp://hdl.handle.net/10261/112373-
dc.description.abstractA series of sp2-iminosugar-type glycomimetics bearing S-linked pseudoglycoside substituents (sulfide, sulfoxide and sulfone derivatives) has been synthesized and evaluated as new potential drugs against the protozoan parasite Leishmania, responsible of leishmaniasis, the second most relevant parasitic disease after malaria. All the prepared compounds share a bicyclic 5N,6O-oxomethylidenenojirimycin glyconelike moiety bearing a substitution pattern of configurational complementarity with the natural a-glucosides and incorporate either an n-octyl or n-dodecyl aglycone-like substituent. Not surprisingly, they behaved as potent to moderate competitive inhibitors of a-glucosidase (inhibition constants, Ki, in the range 1.3 to 447 mM). Evaluation of the antileishmanial activity indicated that the dodecyl pseudoglycosides present a significant antiparasitic activity in intracellular amastigotes of Leishmania donovani, the clinically relevant form of the parasite. The antileishmanial effect seems to be associated with the anticancer and proapoptotic activity of the glycomimetics, but not with the a-glucosidase inhibitory efficiency. The (SS)-configured dodecylsulfoxide derivative 4, exhibiting the most favourable activity/toxicity profile, was further assayed in combination treatment with miltefosine, the first oral antileishmanial drug, using the fixed ratio isobologram method. The interaction between derivative 4 and 0.1, 0.2 and 0.3 mM miltefosine was classified as synergistic, showing combination indices of 0.78, 0.76 and 0.80, respectively. Additionally, a miltefosine resistant Leishmania line and the wild-type strain showed similar susceptibility to derivative 4. The results illustrate the potential of sp2-iminosugar pseudoglycosides as promising prototypes for the development of new therapeutic strategies for leishmaniasises_ES
dc.language.isoenges_ES
dc.publisherRoyal Society of Chemistry (UK)es_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rightsopenAccesses_ES
dc.titleAntileishmanial activity of sp2-iminosugar derivativeses_ES
dc.typeartículoes_ES
dc.identifier.doi10.1039/c5ra02627j-
dc.description.peerreviewedPeer reviewedes_ES
dc.relation.publisherversionhttp://dx.doi.org/10.1039/c5ra02627jes_ES
dc.relation.csices_ES
Appears in Collections:(IIQ) Artículos
Files in This Item:
File Description SizeFormat 
c5ra02627j.pdf362,97 kBAdobe PDFThumbnail
View/Open
Show simple item record
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.