Sesquiterpene lactones as potential therapeutic agents against Naegleria fowleri
Naegleria fowleri is the causative agent the primary amoebic meningoencephalitis (PAM), a fatal disease in more than the 90% of the reported cases that affects the central nervous system. The amoeba infects the nasal cavity of mostly children and young adults who report previous aquatic exposure in warm water sources. The rapid progression of the disease and the lack of effective and safety therapeutic options make the search of new anti-amoebic compounds an urgent issue. In this study, twelve sesquiterpene lactones isolated from the zoanthid Palythoa aff. clavata were tested against the trophozoite stage of Naegleria fowleri. Anhydroartemorin (2) and 1(10)Z,4E,14-acetoxy-costunolide (3) showed the best anti-amoeboid activity values with IC50 23.02 ± 1.26 and 28.34 ± 6.27, respectively. In addition, the mechanisms of programmed cell death induction of these two molecules were evaluated with positive results for both compounds. Finally, a structure-activity relationship was analyzed to reveal the dependence of reactivity and lipophilicity on the biological activity. The log P values of the compounds were calculated to postulate them as good candidates to cross the blood-brain barrier, a limiting factor in the development of new anti-Naegleria treatments. Therefore, the mentioned sesquiterpene lactones could be considered as potential PAM therapeutic options in the future.
Main Authors: | , , , , , , , , , , |
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Format: | artículo biblioteca |
Language: | English |
Published: |
Elsevier BV
2022-02-05
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Subjects: | Naegleria, Palythoa, sesquiterpene lactones, meningoencephalitis, programmed cell death, |
Online Access: | http://hdl.handle.net/10261/303074 http://dx.doi.org/10.13039/501100007757 http://dx.doi.org/10.13039/501100011033 http://dx.doi.org/10.13039/501100000780 http://dx.doi.org/10.13039/501100004587 http://dx.doi.org/10.13039/501100004837 |
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dig-ipna-es-10261-3030742023-03-15T02:43:19Z Sesquiterpene lactones as potential therapeutic agents against Naegleria fowleri Arberas-Jiménez, Íñigo Rizo-Liendo, Aitor Nocchi, Nathália Sifaoui, Inés Chao-Pellicer, Javier Souto, María L. Suárez-Gómez, Blanca DIAZ MARRERO, ANA RAQUEL Fernández, José J. Piñero, José E. Lorenzo-Morales, Jacob Instituto de Salud Carlos III Ministerio de Ciencia e Innovación (España) Agencia Estatal de Investigación (España) Ministerio Español de Salud European Commission Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (España) Cabildo de Tenerife Agencia Canaria de Investigación, Innovación y Sociedad de la Información Naegleria Palythoa sesquiterpene lactones meningoencephalitis programmed cell death Naegleria fowleri is the causative agent the primary amoebic meningoencephalitis (PAM), a fatal disease in more than the 90% of the reported cases that affects the central nervous system. The amoeba infects the nasal cavity of mostly children and young adults who report previous aquatic exposure in warm water sources. The rapid progression of the disease and the lack of effective and safety therapeutic options make the search of new anti-amoebic compounds an urgent issue. In this study, twelve sesquiterpene lactones isolated from the zoanthid Palythoa aff. clavata were tested against the trophozoite stage of Naegleria fowleri. Anhydroartemorin (2) and 1(10)Z,4E,14-acetoxy-costunolide (3) showed the best anti-amoeboid activity values with IC50 23.02 ± 1.26 and 28.34 ± 6.27, respectively. In addition, the mechanisms of programmed cell death induction of these two molecules were evaluated with positive results for both compounds. Finally, a structure-activity relationship was analyzed to reveal the dependence of reactivity and lipophilicity on the biological activity. The log P values of the compounds were calculated to postulate them as good candidates to cross the blood-brain barrier, a limiting factor in the development of new anti-Naegleria treatments. Therefore, the mentioned sesquiterpene lactones could be considered as potential PAM therapeutic options in the future. This work was funded by projects PI18/01380 from Instituto de Salud Carlos III, Spain and RICET (RD16/0027/0001 project) and PID2019–109476RB-C21 (BIOALGRI) (Spanish Ministry of Science, Madrid, Spain; from Programa Redes Temáticas de Investigación Cooperativa, FIS (Ministerio Español de Salud, Madrid, Spain) and FEDER. Consorcio Centro de Investigación Biomédica En Red M.P. (CIBER) de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28006 Madrid, Spain and Cabildo de Tenerife 21/0587 cofunded by MEDI and FDCAN. ARL and IAJ were funded by Agencia Canaria de Investigación, Innovación y Sociedad de la Información (ACIISI). N.N. were funded by the Agustín de Betancourt Programme (Cabildo de Tenerife, TFinnova Programme supported by MEDI and FDCAN funds). Authors acknowledge to Drs. Alberto Brito and Adriana Rodríguez Hernández from Universidad de La Laguna (ULL) the taxonomic classification of biological material, and Dr. Ezequiel Quintana Morales from Instituto de Productos Naturales y Agrobiología, Consejo Superior de Investigaciones Científicas (IPNA-CSIC) for assistance in molecular calculations. Peer reviewed 2023-03-14T10:40:38Z 2023-03-14T10:40:38Z 2022-02-05 artículo Biomedicine & Pharmacotherapy, 12(9), 112694: 1-9 (2022) 0753-3322 http://hdl.handle.net/10261/303074 10.1016/j.biopha.2022.112694 http://dx.doi.org/10.13039/501100007757 http://dx.doi.org/10.13039/501100011033 http://dx.doi.org/10.13039/501100000780 http://dx.doi.org/10.13039/501100004587 http://dx.doi.org/10.13039/501100004837 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.2022.112694 Sí open Elsevier BV |
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Naegleria Palythoa sesquiterpene lactones meningoencephalitis programmed cell death Naegleria Palythoa sesquiterpene lactones meningoencephalitis programmed cell death |
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Naegleria Palythoa sesquiterpene lactones meningoencephalitis programmed cell death Naegleria Palythoa sesquiterpene lactones meningoencephalitis programmed cell death Arberas-Jiménez, Íñigo Rizo-Liendo, Aitor Nocchi, Nathália Sifaoui, Inés Chao-Pellicer, Javier Souto, María L. Suárez-Gómez, Blanca DIAZ MARRERO, ANA RAQUEL Fernández, José J. Piñero, José E. Lorenzo-Morales, Jacob Sesquiterpene lactones as potential therapeutic agents against Naegleria fowleri |
description |
Naegleria fowleri is the causative agent the primary amoebic meningoencephalitis (PAM), a fatal disease in more than the 90% of the reported cases that affects the central nervous system. The amoeba infects the nasal cavity of mostly children and young adults who report previous aquatic exposure in warm water sources. The rapid progression of the disease and the lack of effective and safety therapeutic options make the search of new anti-amoebic compounds an urgent issue. In this study, twelve sesquiterpene lactones isolated from the zoanthid Palythoa aff. clavata were tested against the trophozoite stage of Naegleria fowleri. Anhydroartemorin (2) and 1(10)Z,4E,14-acetoxy-costunolide (3) showed the best anti-amoeboid activity values with IC50 23.02 ± 1.26 and 28.34 ± 6.27, respectively. In addition, the mechanisms of programmed cell death induction of these two molecules were evaluated with positive results for both compounds. Finally, a structure-activity relationship was analyzed to reveal the dependence of reactivity and lipophilicity on the biological activity. The log P values of the compounds were calculated to postulate them as good candidates to cross the blood-brain barrier, a limiting factor in the development of new anti-Naegleria treatments. Therefore, the mentioned sesquiterpene lactones could be considered as potential PAM therapeutic options in the future. |
author2 |
Instituto de Salud Carlos III |
author_facet |
Instituto de Salud Carlos III Arberas-Jiménez, Íñigo Rizo-Liendo, Aitor Nocchi, Nathália Sifaoui, Inés Chao-Pellicer, Javier Souto, María L. Suárez-Gómez, Blanca DIAZ MARRERO, ANA RAQUEL Fernández, José J. Piñero, José E. Lorenzo-Morales, Jacob |
format |
artículo |
topic_facet |
Naegleria Palythoa sesquiterpene lactones meningoencephalitis programmed cell death |
author |
Arberas-Jiménez, Íñigo Rizo-Liendo, Aitor Nocchi, Nathália Sifaoui, Inés Chao-Pellicer, Javier Souto, María L. Suárez-Gómez, Blanca DIAZ MARRERO, ANA RAQUEL Fernández, José J. Piñero, José E. Lorenzo-Morales, Jacob |
author_sort |
Arberas-Jiménez, Íñigo |
title |
Sesquiterpene lactones as potential therapeutic agents against Naegleria fowleri |
title_short |
Sesquiterpene lactones as potential therapeutic agents against Naegleria fowleri |
title_full |
Sesquiterpene lactones as potential therapeutic agents against Naegleria fowleri |
title_fullStr |
Sesquiterpene lactones as potential therapeutic agents against Naegleria fowleri |
title_full_unstemmed |
Sesquiterpene lactones as potential therapeutic agents against Naegleria fowleri |
title_sort |
sesquiterpene lactones as potential therapeutic agents against naegleria fowleri |
publisher |
Elsevier BV |
publishDate |
2022-02-05 |
url |
http://hdl.handle.net/10261/303074 http://dx.doi.org/10.13039/501100007757 http://dx.doi.org/10.13039/501100011033 http://dx.doi.org/10.13039/501100000780 http://dx.doi.org/10.13039/501100004587 http://dx.doi.org/10.13039/501100004837 |
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