Sesquiterpenoids and flavonoids from Inula viscosa induce programmed cell death in kinetoplastids

Neglected tropical diseases such as leishmaniasis and American trypanosomiasis represent an increasing health problem. 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 a...

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Autores: Zeouk, Ikrame, Sifaoui, Ines, López Arencibia, Atteneri, Reyes Batlle, María, Bethencourt Estrella, Carlos Javier, López Bazzocchi, Isabel, Bekhti, Khadija, Lorenzo Morales, Jacob, Jiménez Díaz, Ignacio Antonio, Piñero Barroso, José Enrique
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Institución:Universidad de La Laguna (ULL)
Repositorio:RIULL. Repositorio Institucional de la Universidad de La Laguna
OAI Identifier:oai:riull.ull.es:915/36032
Acceso en línea:http://riull.ull.es/xmlui/handle/915/36032
Access Level:acceso abierto
Palabra clave:Inula viscosa
Leishmanicidal
Trypanocidal
Sesquiterpenoids
Flavonoids
Programmed cell death
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spelling Sesquiterpenoids and flavonoids from Inula viscosa induce programmed cell death in kinetoplastidsZeouk, IkrameSifaoui, InesLópez Arencibia, AtteneriReyes Batlle, MaríaBethencourt Estrella, Carlos JavierLópez Bazzocchi, IsabelBekhti, KhadijaLorenzo Morales, JacobJiménez Díaz, Ignacio AntonioPiñero Barroso, José EnriqueInula viscosaLeishmanicidalTrypanocidalSesquiterpenoidsFlavonoidsProgrammed cell deathNeglected tropical diseases such as leishmaniasis and American trypanosomiasis represent an increasing health problem. 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 to perform a bio-guided fractionation of Inula viscosa (Asteraceae) using in vitro assays against three strains of Leishmania 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 activity against promastigotes of L. donovani, L. amazonensis and epimastigotes of T. cruzi. Their structures were successfully characterized by spectroscopic techniques including 1D and 2D NMR experiments. Furthermore, the main bioactive compounds 4, 5 and 6 displayed higher potency (IC50 values between 0.64 and 2.13 μM) against amastigotes 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 that lactonization or oxidation enhanced the biological profile, suggesting that the hydrophobic moiety was presumably involved in the activity by increasing the affinity and/or cell membrane permeability. In order to get an insight into the mechanism of action of these compounds, programmed cell death (PCD) experiments were performed, 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 interesting scaffold for the development of novel antikinetoplastid agents.202420242020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://riull.ull.es/xmlui/handle/915/36032reponame:RIULL. Repositorio Institucional de la Universidad de La Lagunainstname:Universidad de La Laguna (ULL)InglésBiomedicine & Pharmacotherapy 130 (2020) 110518;Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:riull.ull.es:915/360322026-06-22T13:13:57Z
dc.title.none.fl_str_mv Sesquiterpenoids and flavonoids from Inula viscosa induce programmed cell death in kinetoplastids
title Sesquiterpenoids and flavonoids from Inula viscosa induce programmed cell death in kinetoplastids
spellingShingle Sesquiterpenoids and flavonoids from Inula viscosa induce programmed cell death in kinetoplastids
Zeouk, Ikrame
Inula viscosa
Leishmanicidal
Trypanocidal
Sesquiterpenoids
Flavonoids
Programmed cell death
title_short Sesquiterpenoids and flavonoids from Inula viscosa induce programmed cell death in kinetoplastids
title_full Sesquiterpenoids and flavonoids from Inula viscosa induce programmed cell death in kinetoplastids
title_fullStr Sesquiterpenoids and flavonoids from Inula viscosa induce programmed cell death in kinetoplastids
title_full_unstemmed Sesquiterpenoids and flavonoids from Inula viscosa induce programmed cell death in kinetoplastids
title_sort Sesquiterpenoids and flavonoids from Inula viscosa induce programmed cell death in kinetoplastids
dc.creator.none.fl_str_mv Zeouk, Ikrame
Sifaoui, Ines
López Arencibia, Atteneri
Reyes Batlle, María
Bethencourt Estrella, Carlos Javier
López Bazzocchi, Isabel
Bekhti, Khadija
Lorenzo Morales, Jacob
Jiménez Díaz, Ignacio Antonio
Piñero Barroso, José Enrique
author Zeouk, Ikrame
author_facet Zeouk, Ikrame
Sifaoui, Ines
López Arencibia, Atteneri
Reyes Batlle, María
Bethencourt Estrella, Carlos Javier
López Bazzocchi, Isabel
Bekhti, Khadija
Lorenzo Morales, Jacob
Jiménez Díaz, Ignacio Antonio
Piñero Barroso, José Enrique
author_role author
author2 Sifaoui, Ines
López Arencibia, Atteneri
Reyes Batlle, María
Bethencourt Estrella, Carlos Javier
López Bazzocchi, Isabel
Bekhti, Khadija
Lorenzo Morales, Jacob
Jiménez Díaz, Ignacio Antonio
Piñero Barroso, José Enrique
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Inula viscosa
Leishmanicidal
Trypanocidal
Sesquiterpenoids
Flavonoids
Programmed cell death
topic Inula viscosa
Leishmanicidal
Trypanocidal
Sesquiterpenoids
Flavonoids
Programmed cell death
description Neglected tropical diseases such as leishmaniasis and American trypanosomiasis represent an increasing health problem. 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 to perform a bio-guided fractionation of Inula viscosa (Asteraceae) using in vitro assays against three strains of Leishmania 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 activity against promastigotes of L. donovani, L. amazonensis and epimastigotes of T. cruzi. Their structures were successfully characterized by spectroscopic techniques including 1D and 2D NMR experiments. Furthermore, the main bioactive compounds 4, 5 and 6 displayed higher potency (IC50 values between 0.64 and 2.13 μM) against amastigotes 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 that lactonization or oxidation enhanced the biological profile, suggesting that the hydrophobic moiety was presumably involved in the activity by increasing the affinity and/or cell membrane permeability. In order to get an insight into the mechanism of action of these compounds, programmed cell death (PCD) experiments were performed, 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 interesting scaffold for the development of novel antikinetoplastid agents.
publishDate 2020
dc.date.none.fl_str_mv 2020
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://riull.ull.es/xmlui/handle/915/36032
url http://riull.ull.es/xmlui/handle/915/36032
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Biomedicine & Pharmacotherapy 130 (2020) 110518;
dc.rights.none.fl_str_mv Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:RIULL. Repositorio Institucional de la Universidad de La Laguna
instname:Universidad de La Laguna (ULL)
instname_str Universidad de La Laguna (ULL)
reponame_str RIULL. Repositorio Institucional de la Universidad de La Laguna
collection RIULL. Repositorio Institucional de la Universidad de La Laguna
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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