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Meroterpenoids from Gongolaria abies-marina against Kinetoplastids: In Vitro Activity and Programmed Cell Death Study

Leishmaniasis and Chagas disease affect millions of people worldwide. The available treatments against these parasitic diseases are limited and display multiple undesired effects. The brown alga belonging to the genus Gongolaria has been previously reported as a source of compounds with different bi...

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Autores principales: Nicolás-Hernández, Desirée San, Rodríguez-Expósito, Rubén L., López-Arencibia, Atteneri, Bethencourt-Estrella, Carlos J., Sifaoui, Ines, Salazar-Villatoro, Lizbeth, Omaña-Molina, Maritza, Fernández, José J., Díaz-Marrero, Ana R., Piñero, José E., Lorenzo-Morales, Jacob
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10146491/
https://www.ncbi.nlm.nih.gov/pubmed/37111233
http://dx.doi.org/10.3390/ph16040476
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author Nicolás-Hernández, Desirée San
Rodríguez-Expósito, Rubén L.
López-Arencibia, Atteneri
Bethencourt-Estrella, Carlos J.
Sifaoui, Ines
Salazar-Villatoro, Lizbeth
Omaña-Molina, Maritza
Fernández, José J.
Díaz-Marrero, Ana R.
Piñero, José E.
Lorenzo-Morales, Jacob
author_facet Nicolás-Hernández, Desirée San
Rodríguez-Expósito, Rubén L.
López-Arencibia, Atteneri
Bethencourt-Estrella, Carlos J.
Sifaoui, Ines
Salazar-Villatoro, Lizbeth
Omaña-Molina, Maritza
Fernández, José J.
Díaz-Marrero, Ana R.
Piñero, José E.
Lorenzo-Morales, Jacob
author_sort Nicolás-Hernández, Desirée San
collection PubMed
description Leishmaniasis and Chagas disease affect millions of people worldwide. The available treatments against these parasitic diseases are limited and display multiple undesired effects. The brown alga belonging to the genus Gongolaria has been previously reported as a source of compounds with different biological activities. In a recent study from our group, Gongolaria abies-marine was proven to present antiamebic activity. Hence, this brown alga could be a promising source of interesting molecules for the development of new antiprotozoal drugs. In this study, four meroterpenoids were isolated and purified from a dichloromethane/ethyl acetate crude extract through a bioguided fractionation process targeting kinetoplastids. Moreover, the in vitro activity and toxicity were evaluated, and the induction of programmed cell death was checked in the most active and less toxic compounds, namely gongolarone B (2), 6Z-1′-methoxyamentadione (3) and 1′-methoxyamentadione (4). These meroterpenoids triggered mitochondrial malfunction, oxidative stress, chromatin condensation and alterations of the tubulin network. Furthermore, a transmission electron microscopy (TEM) image analysis showed that meroterpenoids (2–4) induced the formation of autophagy vacuoles and ER and Golgi complex disorganization. The obtained results demonstrated that the mechanisms of action at the cellular level of these compounds were able to induce autophagy as well as an apoptosis-like process in the treated parasites.
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spelling pubmed-101464912023-04-29 Meroterpenoids from Gongolaria abies-marina against Kinetoplastids: In Vitro Activity and Programmed Cell Death Study Nicolás-Hernández, Desirée San Rodríguez-Expósito, Rubén L. López-Arencibia, Atteneri Bethencourt-Estrella, Carlos J. Sifaoui, Ines Salazar-Villatoro, Lizbeth Omaña-Molina, Maritza Fernández, José J. Díaz-Marrero, Ana R. Piñero, José E. Lorenzo-Morales, Jacob Pharmaceuticals (Basel) Article Leishmaniasis and Chagas disease affect millions of people worldwide. The available treatments against these parasitic diseases are limited and display multiple undesired effects. The brown alga belonging to the genus Gongolaria has been previously reported as a source of compounds with different biological activities. In a recent study from our group, Gongolaria abies-marine was proven to present antiamebic activity. Hence, this brown alga could be a promising source of interesting molecules for the development of new antiprotozoal drugs. In this study, four meroterpenoids were isolated and purified from a dichloromethane/ethyl acetate crude extract through a bioguided fractionation process targeting kinetoplastids. Moreover, the in vitro activity and toxicity were evaluated, and the induction of programmed cell death was checked in the most active and less toxic compounds, namely gongolarone B (2), 6Z-1′-methoxyamentadione (3) and 1′-methoxyamentadione (4). These meroterpenoids triggered mitochondrial malfunction, oxidative stress, chromatin condensation and alterations of the tubulin network. Furthermore, a transmission electron microscopy (TEM) image analysis showed that meroterpenoids (2–4) induced the formation of autophagy vacuoles and ER and Golgi complex disorganization. The obtained results demonstrated that the mechanisms of action at the cellular level of these compounds were able to induce autophagy as well as an apoptosis-like process in the treated parasites. MDPI 2023-03-23 /pmc/articles/PMC10146491/ /pubmed/37111233 http://dx.doi.org/10.3390/ph16040476 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nicolás-Hernández, Desirée San
Rodríguez-Expósito, Rubén L.
López-Arencibia, Atteneri
Bethencourt-Estrella, Carlos J.
Sifaoui, Ines
Salazar-Villatoro, Lizbeth
Omaña-Molina, Maritza
Fernández, José J.
Díaz-Marrero, Ana R.
Piñero, José E.
Lorenzo-Morales, Jacob
Meroterpenoids from Gongolaria abies-marina against Kinetoplastids: In Vitro Activity and Programmed Cell Death Study
title Meroterpenoids from Gongolaria abies-marina against Kinetoplastids: In Vitro Activity and Programmed Cell Death Study
title_full Meroterpenoids from Gongolaria abies-marina against Kinetoplastids: In Vitro Activity and Programmed Cell Death Study
title_fullStr Meroterpenoids from Gongolaria abies-marina against Kinetoplastids: In Vitro Activity and Programmed Cell Death Study
title_full_unstemmed Meroterpenoids from Gongolaria abies-marina against Kinetoplastids: In Vitro Activity and Programmed Cell Death Study
title_short Meroterpenoids from Gongolaria abies-marina against Kinetoplastids: In Vitro Activity and Programmed Cell Death Study
title_sort meroterpenoids from gongolaria abies-marina against kinetoplastids: in vitro activity and programmed cell death study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10146491/
https://www.ncbi.nlm.nih.gov/pubmed/37111233
http://dx.doi.org/10.3390/ph16040476
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