RT info:eu-repo/semantics/article
T1 Withanolides fromWithania aristata as Antikinetoplastid Agents through Induction of Programmed Cell Death
A1 López Arencibia, Atteneri
A1 San Nicolás Hernández, Desirée
A1 Bethencourt Estrella, Carlos J.
A1 Sifaoui, Ines
A1 Reyes Batlle, María
A1 Rodríguez Expósito, Rubén L.
A1 Rizo Liendo, Aitor
A1 Lorenzo Morales, Jacob
A1 López Bazzocchi, Isabel
A1 Piñero Barroso, José Enrique
A1 Jiménez Díaz, Ignacio Antonio
K1 Leishmania
K1 Trypanosoma
K1 Withania aristata
K1 withanolides
K1 apoptosis-like
AB Leishmaniasis and American trypanosomiasis are parasitic diseases that cause significantclinical, social and economic impact on the population of tropical and subtropical countries.Their current treatment is limited and presents multiple drawbacks, including high toxicity, high cost,lengthy treatment plans, as well as the emergence of resistant species. Therefore, there is a needto find new lead compounds with high potency against parasites and low toxicity in patients.In the present work, the bioguided fractionation of an endemic plant from the Canary Islands,Withania aristata, led to the identification of withanolide-type metabolites (1–3) with leishmanicidaland trypanocidal activities. Compounds 1 and 3 showed a significant dose-dependent inhibitione ect on the proliferation of L. amazonensis promastigotes and T. cruzi epimastigotes, higher than thereference drugs, miltefosine and benznidazole, respectively. Moreover, compounds 1–3 were morepotent (IC50 0.055–0.663  M) than the reference drug against the intracellular amastigote stage ofL. amazonensis, with a high selectivity index on murine macrophage cells (SI 58.66–216.73). Studies onthe mechanism of death showed that the compounds induced programmed cell death or that whichwas apoptosis-like. The present findings underline the potential of withanolides as novel therapeuticantikinetoplastid agents.
YR 2019
FD 2019
LK http://riull.ull.es/xmlui/handle/915/36072
UL http://riull.ull.es/xmlui/handle/915/36072
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DS Repositorio institucional de la Universidad de La Laguna
RD 12-nov-2024