RT info:eu-repo/semantics/article
T1 Sesquiterpenoids and flavonoids from Inula viscosa induce programmed cell death in kinetoplastids
A1 Zeouk, Ikrame
A1 Sifaoui, Ines
A1 López Arencibia, Atteneri
A1 Reyes Batlle, María
A1 Bethencourt Estrella, Carlos Javier
A1 López Bazzocchi, Isabel
A1 Bekhti, Khadija
A1 Lorenzo Morales, Jacob
A1 Jiménez Díaz, Ignacio Antonio
A1 Piñero Barroso, José Enrique
K1 Inula viscosa
K1 Leishmanicidal
K1 Trypanocidal
K1 Sesquiterpenoids
K1 Flavonoids
K1 Programmed cell death
AB Neglected tropical diseases such as leishmaniasis and American trypanosomiasis represent an increasing healthproblem. Current treatments are not satisfactory which remains an urgent need for novel, cheap and safe chemotherapies.In the course of our ongoing search for new potential anti-protozoal agents, this study aimed toperform a bio-guided fractionation of Inula viscosa (Asteraceae) using in vitro assays against three strains ofLeishmania and Trypanosma genus. Eight known compounds were identified from the ethanolic extract of leaves,sesquiterpenoids (3 and 4) and flavonoids (5 and 6) were characterized as the main bioactive constituents.Sesquiterpene lactones 3 and 4 (IC50 values between 4.99 and 14.26 μM) showed promising antiparasitic activityagainst promastigotes of L. donovani, L. amazonensis and epimastigotes of T. cruzi. Their structures were successfullycharacterized by spectroscopic techniques including 1D and 2D NMR experiments. Furthermore, themain bioactive compounds 4, 5 and 6 displayed higher potency (IC50 values between 0.64 and 2.13 μM) againstamastigotes of L. amazonensis than miltefosine (IC50 3.11 μM), and a low toxicity on macrophages cell line(SI > 45). The analysis of structure-activity relationship (SAR) of the anti-protozoal activity revealed thatlactonization or oxidation enhanced the biological profile, suggesting that the hydrophobic moiety was presumablyinvolved in the activity by increasing the affinity and/or cell membrane permeability. In order to get aninsight into the mechanism of action of these compounds, programmed cell death (PCD) experiments wereperformed, and the obtained results suggest that the reported compounds induced PCD in the treated parasites.These results highlight that sesquiterpenoids and flavonoids from I. viscosa could constitute an interestingscaffold for the development of novel antikinetoplastid agents.
YR 2020
FD 2020
LK http://riull.ull.es/xmlui/handle/915/36032
UL http://riull.ull.es/xmlui/handle/915/36032
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 20-dic-2024