Identification of levothyroxine antichagasic through computer-aided drug repurposing

BELLERA CL; BALCAZAR DE; ALBERCA L; LABRIOLA CA; TALEVI A; CARRILLO C

SCIENTIFIC WORLD JOURNAL, THE

THESCIENTIFICWORLD LTD

Lugar: New York; Año: 2014 vol. 2014 p. 1 - 9

1537-744X

Cruzipain (Cz) is the major cystein 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.