{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:26:32Z","timestamp":1790515592404,"version":"4.1.0"},"reference-count":50,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,11]],"date-time":"2021-12-11T00:00:00Z","timestamp":1639180800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-17-EURE-003"],"award-info":[{"award-number":["ANR-17-EURE-003"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-10-EQPX-29-01"],"award-info":[{"award-number":["ANR-10-EQPX-29-01"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"name":"D\u00e9l\u00e9gation R\u00e9gionale Auvergne-Rh\u00f4ne-Alpes","award":["CPER07_13CIRA"],"award-info":[{"award-number":["CPER07_13CIRA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>FR235222 is a natural tetra-cyclopeptide with a strong inhibition effect on histone deacetylases, effective on mammalian cells as well as on intracellular apicomplexan parasites, such as Toxoplasma gondii, in the tachyzoite and bradyzoite stages. This molecule is characterized by two parts: the zinc-binding group, responsible for the binding to the histone deacetylase, and the cyclic tetrapeptide moiety, which plays a crucial role in cell permeability. Recently, we have shown that the cyclic tetrapeptide coupled with a fluorescent diethyl-amino-coumarin was able to maintain properties of cellular penetration on human cells. Here, we show that this property can be extended to the crossing of the Toxoplasma gondii cystic cell wall and the cell membrane of the parasite in its bradyzoite form, while maintaining a high efficacy as a histone deacetylase inhibitor. The investigation by molecular modeling allows a better understanding of the penetration mechanism.<\/jats:p>","DOI":"10.3390\/molecules26247506","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T01:29:33Z","timestamp":1639358973000},"page":"7506","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Crossing of the Cystic Barriers of Toxoplasma gondii by the Fluorescent Coumarin Tetra-Cyclopeptide"],"prefix":"10.3390","volume":"26","author":[{"given":"C\u00e9line","family":"Dard","sequence":"first","affiliation":[{"name":"Team Host-Pathogen Interactions and Immunity to Infection, Institute for Advanced Biosciences, INSERM, CNRSINSERM U1209, CNRS UMR 5309, Univ. Grenoble Alpes, 38000 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8547-6021","authenticated-orcid":false,"given":"Baptiste","family":"Leforestier","sequence":"additional","affiliation":[{"name":"Team SITH, CNRS UMR 5250, Univ. Grenoble Alpes, CNRS, DCM, 38000 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flaviane","family":"Francisco Hil\u00e1rio","sequence":"additional","affiliation":[{"name":"Team COMET, CNRS UMR 5063, Univ. Grenoble Alpes, CNRS, DPM, 38000 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Dit Mady","family":"Traor\u00e9","sequence":"additional","affiliation":[{"name":"Team COMET, CNRS UMR 5063, Univ. Grenoble Alpes, CNRS, DPM, 38000 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Ange","family":"Lespinasse","sequence":"additional","affiliation":[{"name":"Team COMET, CNRS UMR 5063, Univ. Grenoble Alpes, CNRS, DPM, 38000 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basile","family":"P\u00e9r\u00e8s","sequence":"additional","affiliation":[{"name":"Team COMET, CNRS UMR 5063, Univ. Grenoble Alpes, CNRS, DPM, 38000 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Carmen","family":"Molina","sequence":"additional","affiliation":[{"name":"Team COMET, CNRS UMR 5063, Univ. Grenoble Alpes, CNRS, DPM, 38000 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6974-3724","authenticated-orcid":false,"given":"Rossimiriam","family":"Pereira de Freitas","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica, Universidade Federal de Minas Gerais, Av Pres Ant\u00f4nio Carlos, 6627, Pampulha, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Milet","sequence":"additional","affiliation":[{"name":"Team SITH, CNRS UMR 5250, Univ. Grenoble Alpes, CNRS, DCM, 38000 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9080-7638","authenticated-orcid":false,"given":"Dani\u00e8le","family":"Maubon","sequence":"additional","affiliation":[{"name":"Team Host-Pathogen Interactions and Immunity to Infection, Institute for Advanced Biosciences, INSERM, CNRSINSERM U1209, CNRS UMR 5309, Univ. Grenoble Alpes, 38000 Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1038-9681","authenticated-orcid":false,"given":"Yung-Sing","family":"Wong","sequence":"additional","affiliation":[{"name":"Departamento de Qu\u00edmica, Universidade Federal de Minas Gerais, Av Pres Ant\u00f4nio Carlos, 6627, Pampulha, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/S1471-4922(02)02248-1","article-title":"Toxoplasma Gondii Tachyzoite\u2013Bradyzoite Interconversion","volume":"18","author":"Lyons","year":"2002","journal-title":"Trends Parasitol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1920","DOI":"10.1111\/j.1462-5822.2011.01681.x","article-title":"The Organization of the Wall Filaments and Characterization of the Matrix Structures of Toxoplasma Gondii Cyst Form","volume":"13","author":"Lemgruber","year":"2011","journal-title":"Cell. 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