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dc.contributor.authorSan Nicol´ás Hern´andez, Desir´ee
dc.contributor.authorBethencourt Estrella, Carlos Javier
dc.contributor.authorL´opez Arencibia, Atteneri
dc.contributor.authorHernández Álvarez, Eduardo
dc.contributor.authorSifaoui, Inés
dc.contributor.authorLópez Bazzocchi, Isabel
dc.contributor.authorLorenzo Morales, Jacob
dc.contributor.authorJiménez Díaz, Ignacio Antonio 
dc.contributor.authorPiñero Barroso, José Enrique ¡
dc.date.accessioned2024-01-31T14:15:18Z
dc.date.available2024-01-31T14:15:18Z
dc.date.issued2023
dc.identifier.urihttp://riull.ull.es/xmlui/handle/915/35874
dc.description.abstractCurrent therapies of leishmaniasis and Chagas disease, two of the most widespread neglected tropical diseases, have limited efficacy and toxic side effects. In this regard, natural products play an important role in overcoming the current need for new antiparasitic agents. The present study reports the leishmanicidal and trypanocidal activities of twenty-four known silyl-ether derivatives of withaferin A. Eleven compounds from this series (4, 7, 8, 10, 12, 15, 17, 18, 20, 22 and 25) showed a potent dose-dependent inhibitory effect on the proliferation of Leishmania amazonensis promastigotes and Trypanosoma cruzi epimastigotes respectively, even higher than the references drugs, miltefosine and benznidazole. Among them, the most promising compound, derivative 10, exhibited approximately 34-fold higher leishmanicidal activity and 49-fold higher trypanocidal activity compared to the reference drugs, as well as lower cytotoxicity. Moreover, compounds 4, 7, 10, 12 and 15 were more active than the reference drugs against the amastigote forms of L. amazonensis, presenting a high selectivity index. Assays performed to study the ATP levels, mitochondrial membrane potential, plasma membrane permeability, chromatin condensation, reactive oxygen species and autophagy indicated that these withaferin Asilyl analogs appear to induce events characteristic of apoptosis-like and also autophagy leading to programmed cell death. These findings support the therapeutic potential of withaferin A-related steroids as anti-Leishmania and Trypanosoma agents.es_ES
dc.language.isoenes_ES
dc.relation.ispartofseriesBiomedicine & Pharmacotherapy 157 (2023) 114012;
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.titleWithaferin A-silyl ether analogs as potential anti-kinetoplastid agents targeting the programmed cell deathes_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.identifier.doi10.1016/j.biopha.2022.114012
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES
dc.subject.keywordLeishmaniasises_ES
dc.subject.keywordChagas diseasees_ES
dc.subject.keywordWithaferin Aes_ES
dc.subject.keywordApoptosises_ES
dc.subject.keywordAutophagyes_ES
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersiones_ES


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Attribution-NonCommercial-NoDerivatives 4.0 Internacional
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