{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T07:31:13Z","timestamp":1773300673516,"version":"3.50.1"},"reference-count":46,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2015,6,26]],"date-time":"2015-06-26T00:00:00Z","timestamp":1435276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH-FIRCA","award":["TW008588"],"award-info":[{"award-number":["TW008588"]}]},{"name":"CSIC, UdelaR","award":["625"],"award-info":[{"award-number":["625"]}]},{"name":"FOCEM","award":["[COF 03\/11]"],"award-info":[{"award-number":["[COF 03\/11]"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Parasitic flatworms cause serious infectious diseases that affect humans  and livestock in vast regions of the world, yet there are few effective drugs to treat them. Thioredoxin glutathione reductase (TGR) is an essential enzyme for redox homeostasis in flatworm parasites and a promising pharmacological target. We purified to homogeneity and characterized the TGR from the tapeworm Mesocestoides vogae (syn. M. corti). This purification revealed absence of conventional TR and GR. The glutathione reductase activity of the purified TGR exhibits a hysteretic behavior typical of flatworm TGRs. Consistently, M. vogae genome analysis revealed the presence of a selenocysteine-containing TGR  and absence of conventional TR and GR. M. vogae thioredoxin and glutathione reductase activities were inhibited by 3,4-bis(phenylsulfonyl)-1,2,5-oxadiazole N2-oxide (VL16E), an oxadiazole N-oxide previously identified as an inhibitor of fluke and tapeworm TGRs. Finally, we show that mice experimentally infected with M. vogae tetrathyridia and treated with either praziquantel, the reference drug for flatworm infections, or VL16E exhibited a 28% reduction of intraperitoneal larvae numbers compared to vehicle treated mice. Our results show that oxadiazole N-oxide is a promising chemotype in vivo and highlights the convenience of M. vogae as a model for rapid assessment of tapeworm infections in vivo.<\/jats:p>","DOI":"10.3390\/molecules200711793","type":"journal-article","created":{"date-parts":[[2015,6,26]],"date-time":"2015-06-26T10:24:46Z","timestamp":1435314286000},"page":"11793-11807","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Inhibition of Tapeworm Thioredoxin and Glutathione  Pathways by an Oxadiazole N-Oxide Leads to Reduced Mesocestoides vogae Infection Burden in Mice"],"prefix":"10.3390","volume":"20","author":[{"given":"Vivian","family":"Pasquet","sequence":"first","affiliation":[{"name":"Inmunolog\u00eda, Instituto de Higiene, Facultad de Qu\u00edmica, Universidad de la Rep\u00fablica, Avda, A. Navarro 3051, Montevideo 11400, Uruguay"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugo","family":"Bisio","sequence":"additional","affiliation":[{"name":"Worm Biology Laboratory, Institut Pasteur Montevideo, Mataojo 2020, Montevideo 11400, Uruguay"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gloria","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Grupo de Qu\u00edmica Medicinal, Laboratorio de Qu\u00edmica Org\u00e1nica,  Facultad de Qu\u00edmica-Facultad de Ciencias, Universidad de la Rep\u00fablica, Igu\u00e1 4225,  Montevideo 11400, Uruguay"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Romanelli-Cedrez","sequence":"additional","affiliation":[{"name":"Worm Biology Laboratory, Institut Pasteur Montevideo, Mataojo 2020, Montevideo 11400, Uruguay"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana","family":"Bonilla","sequence":"additional","affiliation":[{"name":"Redox Biology of Trypanosomes Laboratory, Institut Pasteur Montevideo, Mataojo 2020, Montevideo 11400, Uruguay"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenny","family":"Salda\u00f1a","sequence":"additional","affiliation":[{"name":"Laboratorio de Experimentaci\u00f3n Animal, Depto de Ciencias Farmac\u00e9uticas, Facultad de Qu\u00edmica, Universidad de la Rep\u00fablica, Avda. Gral. Flores 2124, Montevideo 11800, Uruguay"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gustavo","family":"Salinas","sequence":"additional","affiliation":[{"name":"Inmunolog\u00eda, Instituto de Higiene, Facultad de Qu\u00edmica, Universidad de la Rep\u00fablica, Avda, A. Navarro 3051, Montevideo 11400, Uruguay"},{"name":"Worm Biology Laboratory, Institut Pasteur Montevideo, Mataojo 2020, Montevideo 11400, Uruguay"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2015,6,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1172\/JCI34261","article-title":"Helminth infections: The great neglected tropical diseases","volume":"118","author":"Hotez","year":"2008","journal-title":"J. Clin. 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