Application of Computer-Aided Drug Repurposing in the Search of New Cruzipain Inhibitors: Discovery of Amiodarone and Bromocriptine Inhibitory Effects.

CAROLINA L. BELLERA, DARÍO E. BALCAZAR, LUCAS ALBERCA, CARLOS A. LABRIOLA, ALAN TALEVI, AND CAROLINA CARRILLO

JOURNAL OF CHEMICAL INFORMATION AND MODELING

AMER CHEMICAL SOC

Lugar: Washington; Año: 2013 vol. 53 p. 2402 - 2408

1549-9596

Cruzipain (Cz) is the major cystein protease of the protozoan Trypanosoma cruzi , etiological agent of Chagas disease. From a 163 compound data set, a 2D-classifier capable of identifying Cz inhibitors was obtained and applied in a virtual screening campaign on the DrugBank database, which compiles FDA-approved and investigational drugs. Fifty-four approved drugs were selected as candidates, four of which were acquired and tested on Cz and T. cruzi epimastigotes. Among them, the antiparkinsonian and antidiabetic drug bromocriptine and the antiarrhythmic amiodarone showed dose-dependent inhibition of Cz and antiproliferative activity on the parasite.