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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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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. |
format | Online Article Text |
id | pubmed-10146491 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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