Application of computer-aided drug repurposing in the search of new cruzipain inhibitors: discovery of amiodarone and bromocriptine inhibitory effects

BELLERA C.; BALCAZAR D.; ALBERCA L.; LABRIOLA C.; CARRILLO C.; TALEVI A.

JOURNAL OF CHEMICAL INFORMATION AND MODELING

AMER CHEMICAL SOC

Lugar: Washington; Año: 2013

1549-9596

Cruzipain (Cz) is the major cystein protease of the protozoan Trypanosoma cruzi, etiological agent of Chagas disease. From a 163-compound dataset, 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. 54 approved drugs were selected as candidates, 4 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.