Logo do repositório
 
Publicação

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

2022Artigo científico Acesso aberto
Ver registo simples
dc.contributor.authorJublot, Delphine
dc.contributor.authorCavaillès, Pierre
dc.contributor.authorKamche, Salima
dc.contributor.authorFrancisco, Denise
dc.contributor.authorFontinha, Diana
dc.contributor.authorPrudêncio, Miguel
dc.contributor.authorGuichou, Jean-Francois
dc.contributor.authorLabesse, Gilles
dc.contributor.authorSereno, Denis
dc.contributor.authorLoeuillet, Corinne
dc.date.accessioned2022-03-29T16:18:08Z
dc.date.available2022-03-29T16:18:08Z
dc.date.issued2022
dc.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/).pt_PT
dc.description.abstractToxoplasmosis 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.pt_PT
dc.description.sponsorshipThis research was funded by IDEX Innovation Grant, UGA, 2017 and The GIS ChemBioFrancept_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationInt J Mol Sci. 2022 Mar 17;23(6):3254pt_PT
dc.identifier.doi10.3390/ijms23063254pt_PT
dc.identifier.eissn1422-0067
dc.identifier.issn1661-6596
dc.identifier.urihttp://hdl.handle.net/10451/52079
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relation.publisherversionhttps://www.mdpi.com/journal/ijmspt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subjectHDACipt_PT
dc.subjectIC50pt_PT
dc.subjectPlasmodiumpt_PT
dc.subjectAnti-Toxoplasma drugpt_PT
dc.subjectMicept_PT
dc.subjectTreatmentpt_PT
dc.titleA Histone Deacetylase (HDAC) inhibitor with pleiotropic in vitro anti-toxoplasma and anti-plasmodium activities controls acute and chronic toxoplasma infection in micept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.issue6pt_PT
oaire.citation.titleInternational Journal of Molecular Sciencespt_PT
oaire.citation.volume23pt_PT
person.familyNameRodrigues Francisco
person.familyNameFontinha
person.familyNamePrudêncio
person.givenNameDenise
person.givenNameDiana
person.givenNameMiguel
person.identifierhttps://scholar.google.pt/citations?user=zduN6wsAAAAJ&hl=pt-PT&oi=ao
person.identifier.ciencia-idC61C-7F84-0375
person.identifier.ciencia-id6A17-C404-F33B
person.identifier.ciencia-id5511-16ED-48E0
person.identifier.orcid0000-0002-0046-648X
person.identifier.orcid0000-0003-1746-6029
person.identifier.scopus-author-id6603561872
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublication98e59108-6dc0-4988-a881-07fd4fa31548
relation.isAuthorOfPublication4fa5980c-148c-4e44-a818-9e8d09245891
relation.isAuthorOfPublication80e4e74d-bf34-4a71-8530-cc3280543b65
relation.isAuthorOfPublication.latestForDiscovery80e4e74d-bf34-4a71-8530-cc3280543b65

Ficheiros

Principais
A mostrar 1 - 1 de 1
Miniatura
Nome:
HDAC.pdf
Tamanho:
1.59 MB
Formato:
Adobe Portable Document Format
Ver/Abrir

Coleções

IMM - Artigos em Revistas Internacionais
FM - Artigos em Revistas Internacionais