title: Identification of levothyroxine antichagasic activity through computer-aided drug repurposing.
abstract: Cruzipain (Cz) is the major cysteine protease of the protozoan Trypanosoma cruzi, 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 T. cruzi 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.
authors.affiliation: Medicinal Chemistry, Department of Biological Sciences, Faculty of Exact Sciences, National University of La Plata, 47 y 115, La Plata (B1900AJI) Buenos Aires, Argentina.
authors.forename: Carolina L
authors.initials: CL
authors.lastname: Bellera
authors.affiliation: Instituto de Ciencia y Tecnología Dr. César Milstein (ICT Milstein), Argentinean National Council of Scientific and Technical Research (CONICET), Saladillo 2468, Ciudad Autónoma de Buenos Aires (C1440FFX), Argentina.
authors.forename: Darío E
authors.initials: DE
authors.lastname: Balcazar
authors.affiliation: Medicinal Chemistry, Department of Biological Sciences, Faculty of Exact Sciences, National University of La Plata, 47 y 115, La Plata (B1900AJI) Buenos Aires, Argentina.
authors.forename: Lucas
authors.initials: L
authors.lastname: Alberca
authors.affiliation: Instituto de Investigaciones Bioquímicas de Buenos Aires, Argentinean National Council of Scientific and Technical Research (CONICET), Avenida Patricias Argentinas 435, Ciudad Autónoma de Buenos Aires (C1405BWE), Argentina.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Labriola
authors.affiliation: Medicinal Chemistry, Department of Biological Sciences, Faculty of Exact Sciences, National University of La Plata, 47 y 115, La Plata (B1900AJI) Buenos Aires, Argentina.
authors.forename: Alan
authors.identifier: 0000-0003-3178-826X
authors.initials: A
authors.lastname: Talevi
authors.affiliation: Instituto de Ciencia y Tecnología Dr. César Milstein (ICT Milstein), Argentinean National Council of Scientific and Technical Research (CONICET), Saladillo 2468, Ciudad Autónoma de Buenos Aires (C1440FFX), Argentina.
authors.forename: Carolina
authors.initials: C
authors.lastname: Carrillo
mesh_terms: D000981:Antiprotozoal Agents / Q000737:chemistry* / Q000494:pharmacology; D020134:Catalytic Domain; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D011485:Protein Binding; D015800:Protozoan Proteins / Q000737:chemistry* / Q000378:metabolism; D013974:Thyroxine / Q000737:chemistry* / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000201:enzymology
chemical_list: D000981:Antiprotozoal Agents; D015853:Cysteine Proteinase Inhibitors; D015800:Protozoan Proteins; D003546:Cysteine Endopeptidases; C063214:cruzipain; D013974:Thyroxine