Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/24755
Title: 4-aminopyridyl-based lead compounds targeting CYP51 prevent spontaneous parasite relapse in a chronic model and improve cardiac pathology in an acute model of Trypanosoma cruzi infection
Authors: Calvet, Claudia Magalhaes
Choi, Jun Yong
Thomas, Diane
Suzuki, Brian
Hirata, Ken
Lostracco-Johnson, Sharon
Mesquita, Liliane Batista de
Nogueira, Alanderson
Batista, Marcelo Meuser
Silva, Tatiana Araujo
Siqueira Neto, Jair Lage
Roush, William R.
Pereira, Mirian Claudia de Souza
McKerrow, James H.
Podust, Larissa M.
Affilliation: University of California San Diego. Skaggs School of Pharmacy and Pharmaceutical Sciences. La Jolla. Center for Discovery and Innovation in Parasitic Diseases. CA, USA / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil.
Scripps Florida. Department of Chemistry. Jupiter, Florida, USA.
University of California San Diego. Skaggs School of Pharmacy and Pharmaceutical Sciences. La Jolla. Center for Discovery and Innovation in Parasitic Diseases. CA, USA.
University of California San Diego. Skaggs School of Pharmacy and Pharmaceutical Sciences. La Jolla. Center for Discovery and Innovation in Parasitic Diseases. CA, USA.
University of California San Diego. Skaggs School of Pharmacy and Pharmaceutical Sciences. La Jolla. Center for Discovery and Innovation in Parasitic Diseases. CA, USA.
University of California San Diego. Skaggs School of Pharmacy and Pharmaceutical Sciences. La Jolla. Center for Discovery and Innovation in Parasitic Diseases. CA, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Fernandes Figueira. Departamento de Anatomia Patológica. Rio de Janeiro, RJ. Brasil .
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil.
University of California San Diego. Skaggs School of Pharmacy and Pharmaceutical Sciences. La Jolla. Center for Discovery and Innovation in Parasitic Diseases. CA, USA.
Scripps Florida. Department of Chemistry. Jupiter, Florida, USA.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil.
University of California San Diego. Skaggs School of Pharmacy and Pharmaceutical Sciences. La Jolla. Center for Discovery and Innovation in Parasitic Diseases. CA, USA.
University of California San Diego. Skaggs School of Pharmacy and Pharmaceutical Sciences. La Jolla. Center for Discovery and Innovation in Parasitic Diseases. CA, USA.
Abstract: Chagas disease, caused by the protozoan Trypanosoma cruzi, is the leading cause of heart failure in Latin America. The clinical treatment of Chagas disease is limited to two 60 year-old drugs, nifurtimox and benznidazole, that have variable efficacy against different strains of the parasite and may lead to severe side effects. CYP51 is an enzyme in the sterol biosynthesis pathway that has been exploited for the development of therapeutics for fungal and parasitic infections. In a target-based drug discovery program guided by x-ray crystallography, we identified the 4-aminopyridyl-based series of CYP51 inhibitors as being efficacious versus T.cruzi in vitro; two of the most potent leads, 9 and 12, have now been evaluated for toxicity and efficacy in mice.
Keywords: Trypanosoma cruzi
Chagas Disease
Treatment
Cardiomiopathy
Infection
keywords: Trypanosoma cruzi
Doença de Chagas
Tratamento
Cardiomiopatias
Infecção
Issue Date: 2017
Publisher: Public Library of Science
Citation: CALVET, Claudia Magalhães; et al. 4-aminopyridyl-based lead compounds targeting CYP51 prevent spontaneous parasite relapse in a chronic model and improve cardiac pathology in an acute model of Trypanosoma cruzi infection. PLOS Neglected Tropical Diseases, v.11, n.12, e0006132, 12p, Dec. 2017.
DOI: 10.1371/journal.pntd.0006132
ISSN: 1935-2727
Copyright: open access
Appears in Collections:IOC - Artigos de Periódicos

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