High-Throughput Screening of Five Compound Libraries for Anthelmintic Activity and Toxicity Leads to the Discovery of Two Flavonoid Compounds

Gastrointestinal nematode infections (GINs) in ruminants are a major constraint to efficient livestock production worldwide. Currently, only a limited number of anthelmintic drugs are available for the control of these infections, but their widespread use in preventive deworming campaigns and the in...

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Autores: Galli, Giulio, Ruiz-Somacarrera, Marta, González del Palacio, Laura, Melcón-Fernández, Estela, González Pérez, Rubén, García Estrada, Carlos, Martinez-Valladares, María, Balaña-Fouce, Rafael
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2025
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositório:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/382506
Acesso em linha:http://hdl.handle.net/10261/382506
Access Level:Acceso aberto
Palavra-chave:Anthelmintic
Chalcone derivatives
Tolfenpyrad
Octenidine
Toxicity
Selective index
Organoid
High-throughput screening
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spelling High-Throughput Screening of Five Compound Libraries for Anthelmintic Activity and Toxicity Leads to the Discovery of Two Flavonoid CompoundsGalli, GiulioRuiz-Somacarrera, MartaGonzález del Palacio, LauraMelcón-Fernández, EstelaGonzález Pérez, RubénGarcía Estrada, CarlosMartinez-Valladares, MaríaBalaña-Fouce, RafaelAnthelminticChalcone derivativesTolfenpyradOctenidineToxicitySelective indexOrganoidHigh-throughput screeningGastrointestinal nematode infections (GINs) in ruminants are a major constraint to efficient livestock production worldwide. Currently, only a limited number of anthelmintic drugs are available for the control of these infections, but their widespread use in preventive deworming campaigns and the incorrect administration of the drugs are responsible for the emergence of resistance. Therefore, new anthelmintic drugs are urgently needed. However, drug discovery methods for new anthelmintics based on GINs isolated from ruminants often have low throughput. In this study, a screening of five commercial collections of chemical compounds, including one collection of anti-infective drugs, three plant-based natural product collections, and one collection from the FDA-approved Chinese Pharmacopoeia, with a total of 2228 molecules, have been carried out in a high-throughput format. In the single slot screen, 32 compounds (1.44% success rate) achieved a >70% motility inhibition rate. Of these, 10 are known anthelmintic drugs, while the remaining 22 were tested against Haemonchus contortus and a resistant strain of Teladorsagia circumcincta. Four compounds (two flavonoids, chalcone and trans-chalcone), and two anti-infectives (octenidine and tolfenpyrad), showed anthelmintic activity with EC50 values below 20 µM, and were further tested for their safety against HepG2 spheroids and mouse intestinal organoids. Trans-chalcone and chalcone emerged as promising candidates for future development, showing selective indexes > 5, while tolfenpyrad and octenidine require careful evaluation due to their toxicity profiles.This publication is part of the R&D project PID2020-119035RB-100, funded by MCIN/AEI/10.13039/501100011033/ and, “ESF Investing in your future”. Grant PRE2021-096909 funded by MCIN/AEI/10.13039/501100011033 and by “ESF Investing in your future”. Grant funded by Consejería de Educación and ESF Investing in your future EDU/1330/2023.Peer reviewedMultidisciplinary Digital Publishing InstituteMinisterio de Ciencia e Innovación (España)Agencia Estatal de Investigación (España)European CommissionConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2025202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/382506reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-119035RB-I00Galli, G.; Ruiz Somacarrera, M.; González del Palacio, L.; Melcón-Fernández, E.; González-Pérez, R.; García-Estrada, C.; Martinez-Valladares, M. ; Balana-Fouce, R.; High throughput screening of five compound libraries for anthelmintic activity and toxicity leads to the discovery of two flavonoid compounds [Dataset], Zenodo; https://doi.org/10.5281/zenodo.14795233https://doi.org/10.3390/ijms26041595Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3825062026-05-22T06:33:51Z
dc.title.none.fl_str_mv High-Throughput Screening of Five Compound Libraries for Anthelmintic Activity and Toxicity Leads to the Discovery of Two Flavonoid Compounds
title High-Throughput Screening of Five Compound Libraries for Anthelmintic Activity and Toxicity Leads to the Discovery of Two Flavonoid Compounds
spellingShingle High-Throughput Screening of Five Compound Libraries for Anthelmintic Activity and Toxicity Leads to the Discovery of Two Flavonoid Compounds
Galli, Giulio
Anthelmintic
Chalcone derivatives
Tolfenpyrad
Octenidine
Toxicity
Selective index
Organoid
High-throughput screening
title_short High-Throughput Screening of Five Compound Libraries for Anthelmintic Activity and Toxicity Leads to the Discovery of Two Flavonoid Compounds
title_full High-Throughput Screening of Five Compound Libraries for Anthelmintic Activity and Toxicity Leads to the Discovery of Two Flavonoid Compounds
title_fullStr High-Throughput Screening of Five Compound Libraries for Anthelmintic Activity and Toxicity Leads to the Discovery of Two Flavonoid Compounds
title_full_unstemmed High-Throughput Screening of Five Compound Libraries for Anthelmintic Activity and Toxicity Leads to the Discovery of Two Flavonoid Compounds
title_sort High-Throughput Screening of Five Compound Libraries for Anthelmintic Activity and Toxicity Leads to the Discovery of Two Flavonoid Compounds
dc.creator.none.fl_str_mv Galli, Giulio
Ruiz-Somacarrera, Marta
González del Palacio, Laura
Melcón-Fernández, Estela
González Pérez, Rubén
García Estrada, Carlos
Martinez-Valladares, María
Balaña-Fouce, Rafael
author Galli, Giulio
author_facet Galli, Giulio
Ruiz-Somacarrera, Marta
González del Palacio, Laura
Melcón-Fernández, Estela
González Pérez, Rubén
García Estrada, Carlos
Martinez-Valladares, María
Balaña-Fouce, Rafael
author_role author
author2 Ruiz-Somacarrera, Marta
González del Palacio, Laura
Melcón-Fernández, Estela
González Pérez, Rubén
García Estrada, Carlos
Martinez-Valladares, María
Balaña-Fouce, Rafael
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
Agencia Estatal de Investigación (España)
European Commission
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Anthelmintic
Chalcone derivatives
Tolfenpyrad
Octenidine
Toxicity
Selective index
Organoid
High-throughput screening
topic Anthelmintic
Chalcone derivatives
Tolfenpyrad
Octenidine
Toxicity
Selective index
Organoid
High-throughput screening
description Gastrointestinal nematode infections (GINs) in ruminants are a major constraint to efficient livestock production worldwide. Currently, only a limited number of anthelmintic drugs are available for the control of these infections, but their widespread use in preventive deworming campaigns and the incorrect administration of the drugs are responsible for the emergence of resistance. Therefore, new anthelmintic drugs are urgently needed. However, drug discovery methods for new anthelmintics based on GINs isolated from ruminants often have low throughput. In this study, a screening of five commercial collections of chemical compounds, including one collection of anti-infective drugs, three plant-based natural product collections, and one collection from the FDA-approved Chinese Pharmacopoeia, with a total of 2228 molecules, have been carried out in a high-throughput format. In the single slot screen, 32 compounds (1.44% success rate) achieved a >70% motility inhibition rate. Of these, 10 are known anthelmintic drugs, while the remaining 22 were tested against Haemonchus contortus and a resistant strain of Teladorsagia circumcincta. Four compounds (two flavonoids, chalcone and trans-chalcone), and two anti-infectives (octenidine and tolfenpyrad), showed anthelmintic activity with EC50 values below 20 µM, and were further tested for their safety against HepG2 spheroids and mouse intestinal organoids. Trans-chalcone and chalcone emerged as promising candidates for future development, showing selective indexes > 5, while tolfenpyrad and octenidine require careful evaluation due to their toxicity profiles.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/382506
url http://hdl.handle.net/10261/382506
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2020-119035RB-I00
Galli, G.; Ruiz Somacarrera, M.; González del Palacio, L.; Melcón-Fernández, E.; González-Pérez, R.; García-Estrada, C.; Martinez-Valladares, M. ; Balana-Fouce, R.; High throughput screening of five compound libraries for anthelmintic activity and toxicity leads to the discovery of two flavonoid compounds [Dataset], Zenodo; https://doi.org/10.5281/zenodo.14795233
https://doi.org/10.3390/ijms26041595
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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