Identification of levothyroxine antichagasic activity through computer-aided drug repurposing

Cruzipain (Cz) is the major cysteine protease of the protozoan <i>Trypanosoma cruzi</i>, etiological agent of Chagas disease. A conformation-independent classifier capable of identifying Cz inhibitors was derived from a 163-compound dataset and later applied in a virtual screening campai...

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Autores principales: Bellera, Carolina Leticia, Balcazar, Darío E., Alberca, Lucas Nicolás, Labriola, Carlos A., Talevi, Alan, Carrillo, Carolina
Formato: Articulo
Lenguaje:Inglés
Publicado: 2014
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Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/85048
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Sumario:Cruzipain (Cz) is the major cysteine protease of the protozoan <i>Trypanosoma cruzi</i>, etiological agent of Chagas disease. A conformation-independent classifier capable of identifying Cz inhibitors was derived from a 163-compound dataset and later applied in a virtual screening campaign on the DrugBank database, which compiles FDA-approved and investigational drugs. 54 approved drugs were selected as candidates, 3 of which were acquired and tested on Cz and <i>T. cruzi</i> epimastigotes proliferation. Among them, levothyroxine, traditionally used in hormone replacement therapy in patients with hypothyroidism, showed dose-dependent inhibition of Cz and antiproliferative activity on the parasite.