The therapeutic potential of novel isobenzofuranones against Naegleria fowleri

The therapeutic potential of novel isobenzofuranones against Naegleria fowleri

The Free-Living Amoeba species, Naegleria fowleri is the causative agent of a lethal encephalitis known as Primary Amoebic Encephalitis (PAM). Moreover, most of the reported cases are often related to swimming and/or diving in aquatic environments. In addition, the current therapeutic options agains...

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Main Authors: Aitor Rizo-Liendo, Iñigo Arberas-Jiménez, Ines Sifaoui, Dimitra Gkolfi, Yiset Santana, Leandro Cotos, David Tejedor, Fernando García-Tellado, José E. Piñero, Jacob Lorenzo-Morales
Format: Article
Language:English
Published: Elsevier 2021-12-01
Series:International Journal for Parasitology: Drugs and Drug Resistance
Subjects:
Naegleria
Therapeutics
Isobenzofuranones
Programmed cell death
Encephalitis
Online Access:http://www.sciencedirect.com/science/article/pii/S2211320721000476
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author Aitor Rizo-Liendo
Iñigo Arberas-Jiménez
Ines Sifaoui
Dimitra Gkolfi
Yiset Santana
Leandro Cotos
David Tejedor
Fernando García-Tellado
José E. Piñero
Jacob Lorenzo-Morales
spellingShingle Aitor Rizo-Liendo
Iñigo Arberas-Jiménez
Ines Sifaoui
Dimitra Gkolfi
Yiset Santana
Leandro Cotos
David Tejedor
Fernando García-Tellado
José E. Piñero
Jacob Lorenzo-Morales
The therapeutic potential of novel isobenzofuranones against Naegleria fowleri
International Journal for Parasitology: Drugs and Drug Resistance
Naegleria
Therapeutics
Isobenzofuranones
Programmed cell death
Encephalitis
author_facet Aitor Rizo-Liendo
Iñigo Arberas-Jiménez
Ines Sifaoui
Dimitra Gkolfi
Yiset Santana
Leandro Cotos
David Tejedor
Fernando García-Tellado
José E. Piñero
Jacob Lorenzo-Morales
author_sort Aitor Rizo-Liendo
title The therapeutic potential of novel isobenzofuranones against Naegleria fowleri
title_short The therapeutic potential of novel isobenzofuranones against Naegleria fowleri
title_full The therapeutic potential of novel isobenzofuranones against Naegleria fowleri
title_fullStr The therapeutic potential of novel isobenzofuranones against Naegleria fowleri
title_full_unstemmed The therapeutic potential of novel isobenzofuranones against Naegleria fowleri
title_sort therapeutic potential of novel isobenzofuranones against naegleria fowleri
publisher Elsevier
series International Journal for Parasitology: Drugs and Drug Resistance
issn 2211-3207
publishDate 2021-12-01
description The Free-Living Amoeba species, Naegleria fowleri is the causative agent of a lethal encephalitis known as Primary Amoebic Encephalitis (PAM). Moreover, most of the reported cases are often related to swimming and/or diving in aquatic environments. In addition, the current therapeutic options against PAM are not fully effective and hence, there is an urgent need to develop novel therapeutic agents against this disease. Previously isobenzofuranones compounds have been reported to present antiprotozoal and antifungal activity among others. However, to the best of our knowledge, these molecules have not been previously tested against N. fowleri. Therefore, the aim of this study was to evaluate the activity of 14 novel isobenzofuranones against this pathogenic amoeba. The most active and less toxic molecules, were assayed in order to check induction of Programmed Cell Death (PCD) in the treated amoebae. The obtained results showed that these molecules were able to eliminate N. fowleri trophozoites and also induced PCD. Therefore, the tested isobenzofuranones could be potential therapeutic candidates for the treatment of PAM.
topic Naegleria
Therapeutics
Isobenzofuranones
Programmed cell death
Encephalitis
url http://www.sciencedirect.com/science/article/pii/S2211320721000476
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spelling doaj-6348baa2cf7d484d8384ea15a9a369202021-10-07T04:24:59ZengElsevierInternational Journal for Parasitology: Drugs and Drug Resistance2211-32072021-12-0117139149The therapeutic potential of novel isobenzofuranones against Naegleria fowleriAitor Rizo-Liendo0Iñigo Arberas-Jiménez1Ines Sifaoui2Dimitra Gkolfi3Yiset Santana4Leandro Cotos5David Tejedor6Fernando García-Tellado7José E. Piñero8Jacob Lorenzo-Morales9Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez, S/N, La Laguna, Tenerife, 38203, Islas Canarias, Spain; Departamento de Obstetricia, Ginecología, Pediatría, Medicina Preventiva y Salud Pública, Toxicología, Medicina Legal y Forense y Parasitología, Universidad De La Laguna, La Laguna, Tenerife, 38203, Islas Canarias, Spain; Red de Investigación Colaborativa en Enfermedades Tropicales (RICET), SpainInstituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez, S/N, La Laguna, Tenerife, 38203, Islas Canarias, Spain; Departamento de Obstetricia, Ginecología, Pediatría, Medicina Preventiva y Salud Pública, Toxicología, Medicina Legal y Forense y Parasitología, Universidad De La Laguna, La Laguna, Tenerife, 38203, Islas Canarias, Spain; Red de Investigación Colaborativa en Enfermedades Tropicales (RICET), SpainInstituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez, S/N, La Laguna, Tenerife, 38203, Islas Canarias, Spain; Departamento de Obstetricia, Ginecología, Pediatría, Medicina Preventiva y Salud Pública, Toxicología, Medicina Legal y Forense y Parasitología, Universidad De La Laguna, La Laguna, Tenerife, 38203, Islas Canarias, Spain; Red de Investigación Colaborativa en Enfermedades Tropicales (RICET), Spain; Consorcio Centro De Investigacion Biomedica En Red M.P. (CIBER) de Enfermedades Infecciosas, Inst. de Salud Carlos III, Madrid, SpainInstituto de Productos Naturales y Agrobiología, Consejo Superior de Investigaciones Científicas, Avda. Fco. Sánchez 3, 38206, La Laguna, Tenerife, Islas Canarias, SpainInstituto de Productos Naturales y Agrobiología, Consejo Superior de Investigaciones Científicas, Avda. Fco. Sánchez 3, 38206, La Laguna, Tenerife, Islas Canarias, SpainInstituto de Productos Naturales y Agrobiología, Consejo Superior de Investigaciones Científicas, Avda. Fco. Sánchez 3, 38206, La Laguna, Tenerife, Islas Canarias, SpainInstituto de Productos Naturales y Agrobiología, Consejo Superior de Investigaciones Científicas, Avda. Fco. Sánchez 3, 38206, La Laguna, Tenerife, Islas Canarias, Spain; Corresponding author.Instituto de Productos Naturales y Agrobiología, Consejo Superior de Investigaciones Científicas, Avda. Fco. Sánchez 3, 38206, La Laguna, Tenerife, Islas Canarias, Spain; Corresponding author.Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez, S/N, La Laguna, Tenerife, 38203, Islas Canarias, Spain; Departamento de Obstetricia, Ginecología, Pediatría, Medicina Preventiva y Salud Pública, Toxicología, Medicina Legal y Forense y Parasitología, Universidad De La Laguna, La Laguna, Tenerife, 38203, Islas Canarias, Spain; Red de Investigación Colaborativa en Enfermedades Tropicales (RICET), Spain; Consorcio Centro De Investigacion Biomedica En Red M.P. (CIBER) de Enfermedades Infecciosas, Inst. de Salud Carlos III, Madrid, Spain; Corresponding author. Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez, S/N, La Laguna, Tenerife, 38203, Islas Canarias, Spain.Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez, S/N, La Laguna, Tenerife, 38203, Islas Canarias, Spain; Departamento de Obstetricia, Ginecología, Pediatría, Medicina Preventiva y Salud Pública, Toxicología, Medicina Legal y Forense y Parasitología, Universidad De La Laguna, La Laguna, Tenerife, 38203, Islas Canarias, Spain; Red de Investigación Colaborativa en Enfermedades Tropicales (RICET), Spain; Consorcio Centro De Investigacion Biomedica En Red M.P. (CIBER) de Enfermedades Infecciosas, Inst. de Salud Carlos III, Madrid, Spain; Corresponding author. Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez, S/N, La Laguna, Tenerife, 38203, Islas Canarias, Spain.The Free-Living Amoeba species, Naegleria fowleri is the causative agent of a lethal encephalitis known as Primary Amoebic Encephalitis (PAM). Moreover, most of the reported cases are often related to swimming and/or diving in aquatic environments. In addition, the current therapeutic options against PAM are not fully effective and hence, there is an urgent need to develop novel therapeutic agents against this disease. Previously isobenzofuranones compounds have been reported to present antiprotozoal and antifungal activity among others. However, to the best of our knowledge, these molecules have not been previously tested against N. fowleri. Therefore, the aim of this study was to evaluate the activity of 14 novel isobenzofuranones against this pathogenic amoeba. The most active and less toxic molecules, were assayed in order to check induction of Programmed Cell Death (PCD) in the treated amoebae. The obtained results showed that these molecules were able to eliminate N. fowleri trophozoites and also induced PCD. Therefore, the tested isobenzofuranones could be potential therapeutic candidates for the treatment of PAM.http://www.sciencedirect.com/science/article/pii/S2211320721000476NaegleriaTherapeuticsIsobenzofuranonesProgrammed cell deathEncephalitis

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