ci400284v_si_002.pdf (388.13 kB)
Application of Computer-Aided Drug Repurposing in the Search of New Cruzipain Inhibitors: Discovery of Amiodarone and Bromocriptine Inhibitory Effects
journal contribution
posted on 2013-09-23, 00:00 authored by Carolina
L. Bellera, Darío E. Balcazar, Lucas Alberca, Carlos A. Labriola, Alan Talevi, Carolina CarrilloCruzipain
(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.