A Histone Deacetylase (HDAC) inhibitor with pleiotropic in vitro anti-toxoplasma and anti-plasmodium activities controls acute and chronic toxoplasma infection in mice

Detalhes bibliográficos
Autor(a) principal: Jublot, Delphine
Data de Publicação: 2022
Outros Autores: Cavaillès, Pierre, Kamche, Salima, Francisco, Denise, Fontinha, Diana, Prudêncio, Miguel, Guichou, Jean-Francois, Labesse, Gilles, Sereno, Denis, Loeuillet, Corinne
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/52079
Resumo: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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spelling A Histone Deacetylase (HDAC) inhibitor with pleiotropic in vitro anti-toxoplasma and anti-plasmodium activities controls acute and chronic toxoplasma infection in miceHDACiIC50PlasmodiumAnti-Toxoplasma drugMiceTreatment© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Toxoplasmosis is a highly prevalent human disease, and virulent strains of this parasite emerge from wild biotopes. Here, we report on the potential of a histone deacetylase (HDAC) inhibitor we previously synthesized, named JF363, to act in vitro against a large panel of Toxoplasma strains, as well as against the liver and blood stages of Plasmodium parasites, the causative agents of malaria. In vivo administration of the drug significantly increases the survival of mice during the acute phase of infection by T. gondii, thus delaying its spreading. We further provide evidence of the compound's efficiency in controlling the formation of cysts in the brain of T. gondii-infected mice. A convincing docking of the JF363 compound in the active site of the five annotated ME49 T. gondii HDACs was performed by extensive sequence-structure comparison modeling. The resulting complexes show a similar mode of binding in the five paralogous structures and a quite similar prediction of affinities in the micromolar range. Altogether, these results pave the way for further development of this compound to treat acute and chronic toxoplasmosis. It also shows promise for the future development of anti-Plasmodium therapeutic interventions.This research was funded by IDEX Innovation Grant, UGA, 2017 and The GIS ChemBioFranceMDPIRepositório da Universidade de LisboaJublot, DelphineCavaillès, PierreKamche, SalimaFrancisco, DeniseFontinha, DianaPrudêncio, MiguelGuichou, Jean-FrancoisLabesse, GillesSereno, DenisLoeuillet, Corinne2022-03-29T16:18:08Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/52079engInt J Mol Sci. 2022 Mar 17;23(6):32541661-659610.3390/ijms230632541422-0067info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:57:07Zoai:repositorio.ul.pt:10451/52079Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:03:13.750212Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv A Histone Deacetylase (HDAC) inhibitor with pleiotropic in vitro anti-toxoplasma and anti-plasmodium activities controls acute and chronic toxoplasma infection in mice
title A Histone Deacetylase (HDAC) inhibitor with pleiotropic in vitro anti-toxoplasma and anti-plasmodium activities controls acute and chronic toxoplasma infection in mice
spellingShingle A Histone Deacetylase (HDAC) inhibitor with pleiotropic in vitro anti-toxoplasma and anti-plasmodium activities controls acute and chronic toxoplasma infection in mice
Jublot, Delphine
HDACi
IC50
Plasmodium
Anti-Toxoplasma drug
Mice
Treatment
title_short A Histone Deacetylase (HDAC) inhibitor with pleiotropic in vitro anti-toxoplasma and anti-plasmodium activities controls acute and chronic toxoplasma infection in mice
title_full A Histone Deacetylase (HDAC) inhibitor with pleiotropic in vitro anti-toxoplasma and anti-plasmodium activities controls acute and chronic toxoplasma infection in mice
title_fullStr A Histone Deacetylase (HDAC) inhibitor with pleiotropic in vitro anti-toxoplasma and anti-plasmodium activities controls acute and chronic toxoplasma infection in mice
title_full_unstemmed A Histone Deacetylase (HDAC) inhibitor with pleiotropic in vitro anti-toxoplasma and anti-plasmodium activities controls acute and chronic toxoplasma infection in mice
title_sort A Histone Deacetylase (HDAC) inhibitor with pleiotropic in vitro anti-toxoplasma and anti-plasmodium activities controls acute and chronic toxoplasma infection in mice
author Jublot, Delphine
author_facet Jublot, Delphine
Cavaillès, Pierre
Kamche, Salima
Francisco, Denise
Fontinha, Diana
Prudêncio, Miguel
Guichou, Jean-Francois
Labesse, Gilles
Sereno, Denis
Loeuillet, Corinne
author_role author
author2 Cavaillès, Pierre
Kamche, Salima
Francisco, Denise
Fontinha, Diana
Prudêncio, Miguel
Guichou, Jean-Francois
Labesse, Gilles
Sereno, Denis
Loeuillet, Corinne
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Jublot, Delphine
Cavaillès, Pierre
Kamche, Salima
Francisco, Denise
Fontinha, Diana
Prudêncio, Miguel
Guichou, Jean-Francois
Labesse, Gilles
Sereno, Denis
Loeuillet, Corinne
dc.subject.por.fl_str_mv HDACi
IC50
Plasmodium
Anti-Toxoplasma drug
Mice
Treatment
topic HDACi
IC50
Plasmodium
Anti-Toxoplasma drug
Mice
Treatment
description © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
publishDate 2022
dc.date.none.fl_str_mv 2022-03-29T16:18:08Z
2022
2022-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/52079
url http://hdl.handle.net/10451/52079
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Int J Mol Sci. 2022 Mar 17;23(6):3254
1661-6596
10.3390/ijms23063254
1422-0067
dc.rights.driver.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 MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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