New benzimidazole derivative compounds with in vitro fasciolicidal properties

[EN] Background: Control of the zoonotic food-borne parasite Fasciola hepatica remains a major challenge in humans and livestock. It is estimated that annual economic losses due to fasciolosis can reach US$3.2 billion in agriculture and livestock. Moreover, the wide distribution of drug-resistant pa...

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Autores: Valderas García, Elora, Castilla Gómez de Agüero, Verónica, González del Palacio, Laura, Galli, Giulio, Escala, Nerea, Ruiz Somacarrera, Marta, González Warleta, Marta, Olmo, Esther del, Balaña Fouce, Rafael, Martínez Valladares, María
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Universidad de León
Repositorio:BULERIA. Repositorio Institucional de la Universidad de León
OAI Identifier:oai:buleria.unileon.es:10612/25802
Acceso en línea:https://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-024-06224-6
https://hdl.handle.net/10612/25802
Access Level:acceso abierto
Palabra clave:Sanidad animal
Veterinaria
Fasciola hepatica
Benzimidazole
Anthelmintic resistance
Zoonotic disease
2401.12 Parasitología Animal
3109.08 Farmacología
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oai_identifier_str oai:buleria.unileon.es:10612/25802
network_acronym_str ES
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spelling New benzimidazole derivative compounds with in vitro fasciolicidal propertiesValderas García, EloraCastilla Gómez de Agüero, VerónicaGonzález del Palacio, LauraGalli, GiulioEscala, NereaRuiz Somacarrera, MartaGonzález Warleta, MartaOlmo, Esther delBalaña Fouce, RafaelMartínez Valladares, MaríaSanidad animalVeterinariaFasciola hepaticaBenzimidazoleAnthelmintic resistanceZoonotic disease2401.12 Parasitología Animal3109.08 Farmacología[EN] Background: Control of the zoonotic food-borne parasite Fasciola hepatica remains a major challenge in humans and livestock. It is estimated that annual economic losses due to fasciolosis can reach US$3.2 billion in agriculture and livestock. Moreover, the wide distribution of drug-resistant parasite populations and the absence of a vaccine threaten sustainable control, reinforcing the need for novel flukicides. Methods: The present work analyses the flukicidal activity of a total of 70 benzimidazole derivatives on different stages of F. hepatica. With the aim to select the most potent ones, and screenings were first performed on eggs at decreasing concentrations ranging from 50 to 5 µM and then on adult worms at 10 µM. Only the most effective compounds were also evaluated using a resistant isolate of the parasite. Results: After the first screenings at 50 and 10 µM, four hit compounds (BZD31, BZD46, BZD56, and BZD59) were selected and progressed to the next assays. At 5 µM, all hit compounds showed ovicidal activities higher than 71% on the susceptible isolate, but only BZD31 remained considerably active (53%) when they were tested on an albendazol-resistant isolate, even with values superior to the reference drug, albendazole sulfoxide. On the other hand, BZD59 displayed a high motility inhibition when tested on adult worms from an albendazole-resistant isolate after 72 h of incubation. Conclusions: BZD31 and BZD59 compounds could be promising candidates for the development of fasciolicidal compounds or as starting point for the new synthesis of structure-related compoundsSIFinancial support came from PID2020-119035RB-100 funded by MCIN/AEI/10.13039/501100011033 and, by “ERDF A way of making Europe”. EVG was funded by European Union Next Generation EU/PRTR (Margarita Salas Grant for the training of young doctors); VCGA and LGDP are recipients of Junta de Castilla y León (JCyL) grants (LE082-18, LE096-20, respectively); GG was funded by PRE2021-096909, grant funded by MCIN/AEI/10.13039/501100011033 and, by “ESF Investing in your future”BioMed CentralSanidad AnimalFacultad de Veterinaria2024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-024-06224-6https://hdl.handle.net/10612/25802reponame:BULERIA. Repositorio Institucional de la Universidad de Leóninstname:Universidad de LeónIngléshttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:buleria.unileon.es:10612/258022026-06-24T12:43:27Z
dc.title.none.fl_str_mv New benzimidazole derivative compounds with in vitro fasciolicidal properties
title New benzimidazole derivative compounds with in vitro fasciolicidal properties
spellingShingle New benzimidazole derivative compounds with in vitro fasciolicidal properties
Valderas García, Elora
Sanidad animal
Veterinaria
Fasciola hepatica
Benzimidazole
Anthelmintic resistance
Zoonotic disease
2401.12 Parasitología Animal
3109.08 Farmacología
title_short New benzimidazole derivative compounds with in vitro fasciolicidal properties
title_full New benzimidazole derivative compounds with in vitro fasciolicidal properties
title_fullStr New benzimidazole derivative compounds with in vitro fasciolicidal properties
title_full_unstemmed New benzimidazole derivative compounds with in vitro fasciolicidal properties
title_sort New benzimidazole derivative compounds with in vitro fasciolicidal properties
dc.creator.none.fl_str_mv Valderas García, Elora
Castilla Gómez de Agüero, Verónica
González del Palacio, Laura
Galli, Giulio
Escala, Nerea
Ruiz Somacarrera, Marta
González Warleta, Marta
Olmo, Esther del
Balaña Fouce, Rafael
Martínez Valladares, María
author Valderas García, Elora
author_facet Valderas García, Elora
Castilla Gómez de Agüero, Verónica
González del Palacio, Laura
Galli, Giulio
Escala, Nerea
Ruiz Somacarrera, Marta
González Warleta, Marta
Olmo, Esther del
Balaña Fouce, Rafael
Martínez Valladares, María
author_role author
author2 Castilla Gómez de Agüero, Verónica
González del Palacio, Laura
Galli, Giulio
Escala, Nerea
Ruiz Somacarrera, Marta
González Warleta, Marta
Olmo, Esther del
Balaña Fouce, Rafael
Martínez Valladares, María
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Sanidad Animal
Facultad de Veterinaria
dc.subject.none.fl_str_mv Sanidad animal
Veterinaria
Fasciola hepatica
Benzimidazole
Anthelmintic resistance
Zoonotic disease
2401.12 Parasitología Animal
3109.08 Farmacología
topic Sanidad animal
Veterinaria
Fasciola hepatica
Benzimidazole
Anthelmintic resistance
Zoonotic disease
2401.12 Parasitología Animal
3109.08 Farmacología
description [EN] Background: Control of the zoonotic food-borne parasite Fasciola hepatica remains a major challenge in humans and livestock. It is estimated that annual economic losses due to fasciolosis can reach US$3.2 billion in agriculture and livestock. Moreover, the wide distribution of drug-resistant parasite populations and the absence of a vaccine threaten sustainable control, reinforcing the need for novel flukicides. Methods: The present work analyses the flukicidal activity of a total of 70 benzimidazole derivatives on different stages of F. hepatica. With the aim to select the most potent ones, and screenings were first performed on eggs at decreasing concentrations ranging from 50 to 5 µM and then on adult worms at 10 µM. Only the most effective compounds were also evaluated using a resistant isolate of the parasite. Results: After the first screenings at 50 and 10 µM, four hit compounds (BZD31, BZD46, BZD56, and BZD59) were selected and progressed to the next assays. At 5 µM, all hit compounds showed ovicidal activities higher than 71% on the susceptible isolate, but only BZD31 remained considerably active (53%) when they were tested on an albendazol-resistant isolate, even with values superior to the reference drug, albendazole sulfoxide. On the other hand, BZD59 displayed a high motility inhibition when tested on adult worms from an albendazole-resistant isolate after 72 h of incubation. Conclusions: BZD31 and BZD59 compounds could be promising candidates for the development of fasciolicidal compounds or as starting point for the new synthesis of structure-related compounds
publishDate 2024
dc.date.none.fl_str_mv 2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-024-06224-6
https://hdl.handle.net/10612/25802
url https://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-024-06224-6
https://hdl.handle.net/10612/25802
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv reponame:BULERIA. Repositorio Institucional de la Universidad de León
instname:Universidad de León
instname_str Universidad de León
reponame_str BULERIA. Repositorio Institucional de la Universidad de León
collection BULERIA. Repositorio Institucional de la Universidad de León
repository.name.fl_str_mv
repository.mail.fl_str_mv
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