title: Application of computer-aided drug repurposing in the search of new cruzipain inhibitors: discovery of amiodarone and bromocriptine inhibitory effects.
abstract: 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.
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.forename: Darío E
authors.initials: DE
authors.lastname: Balcazar
authors.forename: Lucas
authors.initials: L
authors.lastname: Alberca
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Labriola
authors.forename: Alan
authors.initials: A
authors.lastname: Talevi
authors.forename: Carolina
authors.initials: C
authors.lastname: Carrillo
mesh_terms: D000638:Amiodarone / Q000494:pharmacology*; D001971:Bromocriptine / Q000494:pharmacology*; D017076:Computer-Aided Design; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D058492:Drug Repositioning / Q000379:methods*; D015800:Protozoan Proteins; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development
chemical_list: D015853:Cysteine Proteinase Inhibitors; D015800:Protozoan Proteins; D001971:Bromocriptine; D003546:Cysteine Endopeptidases; C063214:cruzipain; D000638:Amiodarone