title: In vivo and in vitro auranofin activity against Trypanosoma cruzi: Possible new uses for an old drug.
abstract: Chagas disease, Sleeping Sickness, Nagana and Leishmaniasis are serious infections caused by protozoa of the order Kinetoplastidae. They were described over a century ago by seminal work of different physician-researchers and, despite the initial discoveries, few drugs have been made available for the treatment of these infections. The drugs available present serious efficacy and toxicity problems. Moreover, the emergence of resistant strains has rendered the development of novel chemotherapeutic strategies a priority. Auranofin is currently in use to treat rheumatoid arthritis in humans. Previous reports showed that this compound presents activity against Trypanosoma brucei and Leishmania cells. In Trypanosoma cruzi cells, auranofin resulted in a more potent compound than benznidazole in vitro when tested in different DTUs. In vivo experiments, although not decreasing T. cruzi parasitemia, decreases host mortality. Therefore, we propose auranofin as a potential alternative for a new chemotherapy in Chagas disease with the added advantage of already being approved for use in humans.
authors.affiliation: Instituto de Física de São Carlos, Universidade de São Paulo, Caixa Postal 369, 13560-590, São Carlos, SP, Brazil.
authors.forename: Marco Túlio Alves
authors.initials: MT
authors.lastname: da Silva
authors.affiliation: Instituto de Física de São Carlos, Universidade de São Paulo, Caixa Postal 369, 13560-590, São Carlos, SP, Brazil.
authors.forename: Izaltina
authors.initials: I
authors.lastname: Silva-Jardim
authors.affiliation: Instituto de Física de São Carlos, Universidade de São Paulo, Caixa Postal 369, 13560-590, São Carlos, SP, Brazil.
authors.forename: Gisele Bulhões
authors.initials: GB
authors.lastname: Portapilla
authors.affiliation: Instituto de Física de São Carlos, Universidade de São Paulo, Caixa Postal 369, 13560-590, São Carlos, SP, Brazil.
authors.forename: Gustavo Machado Alvares
authors.initials: GM
authors.lastname: de Lima
authors.affiliation: Instituto de Física de São Carlos, Universidade de São Paulo, Caixa Postal 369, 13560-590, São Carlos, SP, Brazil; Departamento de Genética e Evolução, Universidade Federal de São Carlos, São Carlos, Brazil.
authors.forename: Fernanda Cristina
authors.initials: FC
authors.lastname: Costa
authors.affiliation: Departamento de Morfologia e Patologia, Universidade Federal de São Carlos, caixa postal 676, 13565-905, São Carlos, SP, Brazil.
authors.forename: Fernanda de Freitas
authors.initials: Fde F
authors.lastname: Anibal
authors.affiliation: Instituto de Física de São Carlos, Universidade de São Paulo, Caixa Postal 369, 13560-590, São Carlos, SP, Brazil; Departamento de Genética e Evolução, Universidade Federal de São Carlos, São Carlos, Brazil. Electronic address: thiemann@ifsc.usp.br.
authors.forename: Otavio Henrique
authors.initials: OH
authors.lastname: Thiemann
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001310:Auranofin / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D014355:Chagas Disease / Q000188:drug therapy* / Q000469:parasitology; D005260:Female; D005347:Fibroblasts / Q000469:parasitology; D006801:Humans; D020128:Inhibitory Concentration 50; D007928:Lethal Dose 50; D051379:Mice; D008807:Mice, Inbred BALB C; D009593:Nitroimidazoles / Q000494:pharmacology; D018512:Parasitemia / Q000188:drug therapy / Q000469:parasitology; D011897:Random Allocation; D013047:Specific Pathogen-Free Organisms; D014344:Trypanocidal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D018501:Antirheumatic Agents; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; D001310:Auranofin; C009999:benzonidazole
keywords: Auranofin; Chemotherapy; Trypanosoma cruzi