Gongolarones as antiamoeboid chemical scaffold
Free Living Amoeba (FLA) infections caused by Acanthamoeba genus include chronic nervous system diseases such as Granulomatous Amoebic Encephalitis (GAE), or a severe eye infection known as Acanthamoeba keratitis (AK). Current studies focused on therapy against these diseases are aiming to find novel compounds with amoebicidal activity and low toxicity to human tissues. Brown algae, such as Gongolaria abies-marina (previously known as Cystoseira abies-marina, S.G. Gmelin), presents bioactive molecules of interest, including some with antiprotozoal activity. In this study, six meroterpenoids were isolated and purified from the species Gongolaria abies-marina. Gongolarones A (1), B (2) and C (3) were identified as new compounds. Additionally, cystomexicone B (4), 1′-methoxyamentadione (5) and 6Z-1′-methoxyamentadione (6) were isolated. All compounds exhibited amoebicidal activity against Acanthamoeba castellanii Neff, A. polyphaga and A. griffini strains. Gongolarones A (1) and C (3) showed the lowest IC50 values against the two stages of these amoebae (trophozoite and cyst). Structure-activity relationship revealed that the cyclization by ether formation from C-12 to C-15 of 1, and the isomerization Δ2 t to Δ3 t of 3, increased the antiamoeboid activity of both compounds. Furthermore, gongolarones A (1) and C (3) triggered chromatin condensation, mitochondrial malfunction, oxidative stress, and disorganization of the tubulin-actin cytoskeleton in treated trophozoites. Moreover, transmission electron microscopy (TEM) images analysis revealed that compounds 1 and 3 induced autophagy process and inhibited the encystation process. All those results suggest that both compounds could induce programmed cell death (PCD) in Acanthamoeba.
Main Authors: | , , , , , , , , , , , |
---|---|
Other Authors: | |
Format: | artículo biblioteca |
Language: | English |
Published: |
Elsevier BV
2023-01-09
|
Subjects: | Acanthamoeba spp., gongolarones, meroterpenoid, gongolaria abies-marina, programmed cell death, autophagy, |
Online Access: | http://hdl.handle.net/10261/305393 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
id |
dig-ipna-es-10261-305393 |
---|---|
record_format |
koha |
institution |
IPNA ES |
collection |
DSpace |
country |
España |
countrycode |
ES |
component |
Bibliográfico |
access |
En linea |
databasecode |
dig-ipna-es |
tag |
biblioteca |
region |
Europa del Sur |
libraryname |
Biblioteca del IPNA España |
language |
English |
topic |
Acanthamoeba spp. gongolarones meroterpenoid gongolaria abies-marina programmed cell death autophagy Acanthamoeba spp. gongolarones meroterpenoid gongolaria abies-marina programmed cell death autophagy |
spellingShingle |
Acanthamoeba spp. gongolarones meroterpenoid gongolaria abies-marina programmed cell death autophagy Acanthamoeba spp. gongolarones meroterpenoid gongolaria abies-marina programmed cell death autophagy Rodríguez-Expósito, Rubén L. San Nicolás-Hernández, Desirée Sifaoui, Ines Cuadrado, Cristina Salazar-Villatoro, Lizbeth Reyes-Batlle, María Hernández Daranas, Antonio Omaña-Molina, Maritza Fernández, José J. DIAZ MARRERO, ANA RAQUEL Piñero, José E. Lorenzo-Morales, Jacob Gongolarones as antiamoeboid chemical scaffold |
description |
Free Living Amoeba (FLA) infections caused by Acanthamoeba genus include chronic nervous system diseases such as Granulomatous Amoebic Encephalitis (GAE), or a severe eye infection known as Acanthamoeba keratitis (AK). Current studies focused on therapy against these diseases are aiming to find novel compounds with amoebicidal activity and low toxicity to human tissues. Brown algae, such as Gongolaria abies-marina (previously known as Cystoseira abies-marina, S.G. Gmelin), presents bioactive molecules of interest, including some with antiprotozoal activity. In this study, six meroterpenoids were isolated and purified from the species Gongolaria abies-marina. Gongolarones A (1), B (2) and C (3) were identified as new compounds. Additionally, cystomexicone B (4), 1′-methoxyamentadione (5) and 6Z-1′-methoxyamentadione (6) were isolated. All compounds exhibited amoebicidal activity against Acanthamoeba castellanii Neff, A. polyphaga and A. griffini strains. Gongolarones A (1) and C (3) showed the lowest IC50 values against the two stages of these amoebae (trophozoite and cyst). Structure-activity relationship revealed that the cyclization by ether formation from C-12 to C-15 of 1, and the isomerization Δ2 t to Δ3 t of 3, increased the antiamoeboid activity of both compounds. Furthermore, gongolarones A (1) and C (3) triggered chromatin condensation, mitochondrial malfunction, oxidative stress, and disorganization of the tubulin-actin cytoskeleton in treated trophozoites. Moreover, transmission electron microscopy (TEM) images analysis revealed that compounds 1 and 3 induced autophagy process and inhibited the encystation process. All those results suggest that both compounds could induce programmed cell death (PCD) in Acanthamoeba. |
author2 |
Ministerio de Ciencia e Innovación (España) |
author_facet |
Ministerio de Ciencia e Innovación (España) Rodríguez-Expósito, Rubén L. San Nicolás-Hernández, Desirée Sifaoui, Ines Cuadrado, Cristina Salazar-Villatoro, Lizbeth Reyes-Batlle, María Hernández Daranas, Antonio Omaña-Molina, Maritza Fernández, José J. DIAZ MARRERO, ANA RAQUEL Piñero, José E. Lorenzo-Morales, Jacob |
format |
artículo |
topic_facet |
Acanthamoeba spp. gongolarones meroterpenoid gongolaria abies-marina programmed cell death autophagy |
author |
Rodríguez-Expósito, Rubén L. San Nicolás-Hernández, Desirée Sifaoui, Ines Cuadrado, Cristina Salazar-Villatoro, Lizbeth Reyes-Batlle, María Hernández Daranas, Antonio Omaña-Molina, Maritza Fernández, José J. DIAZ MARRERO, ANA RAQUEL Piñero, José E. Lorenzo-Morales, Jacob |
author_sort |
Rodríguez-Expósito, Rubén L. |
title |
Gongolarones as antiamoeboid chemical scaffold |
title_short |
Gongolarones as antiamoeboid chemical scaffold |
title_full |
Gongolarones as antiamoeboid chemical scaffold |
title_fullStr |
Gongolarones as antiamoeboid chemical scaffold |
title_full_unstemmed |
Gongolarones as antiamoeboid chemical scaffold |
title_sort |
gongolarones as antiamoeboid chemical scaffold |
publisher |
Elsevier BV |
publishDate |
2023-01-09 |
url |
http://hdl.handle.net/10261/305393 |
work_keys_str_mv |
AT rodriguezexpositorubenl gongolaronesasantiamoeboidchemicalscaffold AT sannicolashernandezdesiree gongolaronesasantiamoeboidchemicalscaffold AT sifaouiines gongolaronesasantiamoeboidchemicalscaffold AT cuadradocristina gongolaronesasantiamoeboidchemicalscaffold AT salazarvillatorolizbeth gongolaronesasantiamoeboidchemicalscaffold AT reyesbatllemaria gongolaronesasantiamoeboidchemicalscaffold AT hernandezdaranasantonio gongolaronesasantiamoeboidchemicalscaffold AT omanamolinamaritza gongolaronesasantiamoeboidchemicalscaffold AT fernandezjosej gongolaronesasantiamoeboidchemicalscaffold AT diazmarreroanaraquel gongolaronesasantiamoeboidchemicalscaffold AT pinerojosee gongolaronesasantiamoeboidchemicalscaffold AT lorenzomoralesjacob gongolaronesasantiamoeboidchemicalscaffold |
_version_ |
1777669923840983040 |
spelling |
dig-ipna-es-10261-3053932023-04-03T09:56:49Z Gongolarones as antiamoeboid chemical scaffold Rodríguez-Expósito, Rubén L. San Nicolás-Hernández, Desirée Sifaoui, Ines Cuadrado, Cristina Salazar-Villatoro, Lizbeth Reyes-Batlle, María Hernández Daranas, Antonio Omaña-Molina, Maritza Fernández, José J. DIAZ MARRERO, ANA RAQUEL Piñero, José E. Lorenzo-Morales, Jacob Ministerio de Ciencia e Innovación (España) Caja Canarias Fundación "la Caixa" Red de Investigación Cooperativa en Enfermedades Tropicales (España) Consorcio Centro de Investigación Biomédica en Red Área de Enfermedades Infecciosas Instituto de Salud Carlos III Cabildo de Tenerife Agencia Canaria de Investigación, Innovación y Sociedad de la Información European Commission Universidad de La Laguna Facultad de Estudios Superiores Iztacala Acanthamoeba spp. gongolarones meroterpenoid gongolaria abies-marina programmed cell death autophagy Free Living Amoeba (FLA) infections caused by Acanthamoeba genus include chronic nervous system diseases such as Granulomatous Amoebic Encephalitis (GAE), or a severe eye infection known as Acanthamoeba keratitis (AK). Current studies focused on therapy against these diseases are aiming to find novel compounds with amoebicidal activity and low toxicity to human tissues. Brown algae, such as Gongolaria abies-marina (previously known as Cystoseira abies-marina, S.G. Gmelin), presents bioactive molecules of interest, including some with antiprotozoal activity. In this study, six meroterpenoids were isolated and purified from the species Gongolaria abies-marina. Gongolarones A (1), B (2) and C (3) were identified as new compounds. Additionally, cystomexicone B (4), 1′-methoxyamentadione (5) and 6Z-1′-methoxyamentadione (6) were isolated. All compounds exhibited amoebicidal activity against Acanthamoeba castellanii Neff, A. polyphaga and A. griffini strains. Gongolarones A (1) and C (3) showed the lowest IC50 values against the two stages of these amoebae (trophozoite and cyst). Structure-activity relationship revealed that the cyclization by ether formation from C-12 to C-15 of 1, and the isomerization Δ2 t to Δ3 t of 3, increased the antiamoeboid activity of both compounds. Furthermore, gongolarones A (1) and C (3) triggered chromatin condensation, mitochondrial malfunction, oxidative stress, and disorganization of the tubulin-actin cytoskeleton in treated trophozoites. Moreover, transmission electron microscopy (TEM) images analysis revealed that compounds 1 and 3 induced autophagy process and inhibited the encystation process. All those results suggest that both compounds could induce programmed cell death (PCD) in Acanthamoeba. This study was supported funded by projects PID2019-109476RB-C21 (BIOALGRI) (Spanish Ministry of Science), Madrid, Spain; Fundación CajaCanarias–Fundación Bancaria “La Caixa” (2019SP52). Red de Investigación Cooperativa en Enfermedades Tropicales (RICET), Spain (project no. RD16/0027/0001 of the programe of Redes Temáticas de Investigación Cooperativa, FIS). Consorcio Centro de Investigación Biomédica en Red (CIBER), Área de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029, Madrid, Spain (CB21/13/00100). Project No. 21/0587 funded by the Cabildo de Tenerife, Tenerife innova, Marco Estratégico de Desarrollo Insular (MEDI) and Fondo de Desarrollo de Canarias (FDCAN). Project number ProID2021010118 funded by Agencia Canaria de Investigación, Innovación y Sociedad de la Información (ACIISI). RLRE was funded by a grant from ACIISI cofunded by Fondo Social Europeo (FSE) and FEDER, (TESIS2020010117). MOM was supported by the Programa de Apoyos para la Superación del Personal Académico de la UNAM (PASPA 2021) for carrying out the research stay between the Universidad de La Laguna and la Facultad de Estudios Superiores Iztacala. Peer reviewed 2023-04-03T09:56:49Z 2023-04-03T09:56:49Z 2023-01-09 artículo Biomedicine & Pharmacotherapy, 158, 114185: 1-23 (2023) 0753-3322 http://hdl.handle.net/10261/305393 10.1016/j.biopha.2022.114185 en #PLACEHOLDER_PARENT_METADATA_VALUE# info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-109476RB-C21/ES/MOLECULAS BIOACTIVAS DE MICROALGAS MARINAS/ Publisher's version https://doi.org/10.1016/j.biopha.2022.114185 Sí open Elsevier BV |