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
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2017 |
| Outros Autores: | , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/24755 |
Resumo: | 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. |
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Calvet, Claudia MagalhaesChoi, Jun YongThomas, DianeSuzuki, BrianHirata, KenLostracco-Johnson, SharonMesquita, Liliane Batista deNogueira, AlandersonBatista, Marcelo MeuserSilva, Tatiana AraujoSiqueira Neto, Jair LageRoush, William R.Pereira, Mirian Claudia de SouzaMcKerrow, James H.Podust, Larissa M.2018-02-08T10:38:50Z2018-02-08T10:38:50Z2017CALVET, 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. 2017.1935-2727https://www.arca.fiocruz.br/handle/icict/2475510.1371/journal.pntd.00061321935-2735engPublic Library of ScienceTrypanosoma cruziDoença de ChagasTratamentoCardiomiopatiasInfecçãoTrypanosoma cruziChagas DiseaseTreatmentCardiomiopathyInfection4-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 infectioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversity 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.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.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/24755/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALliliane_mesquita_etal_IOC_2017.pdfliliane_mesquita_etal_IOC_2017.pdfapplication/pdf18910960https://www.arca.fiocruz.br/bitstream/icict/24755/2/liliane_mesquita_etal_IOC_2017.pdfafaf248225b096e6c890adb96cbd17f7MD52TEXTliliane_mesquita_etal_IOC_2017.pdf.txtliliane_mesquita_etal_IOC_2017.pdf.txtExtracted 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| dc.title.pt_BR.fl_str_mv |
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 |
| 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 |
| spellingShingle |
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 Calvet, Claudia Magalhaes Trypanosoma cruzi Doença de Chagas Tratamento Cardiomiopatias Infecção Trypanosoma cruzi Chagas Disease Treatment Cardiomiopathy Infection |
| title_short |
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 |
| title_full |
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 |
| title_fullStr |
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 |
| title_full_unstemmed |
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 |
| title_sort |
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 |
| author |
Calvet, Claudia Magalhaes |
| author_facet |
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. |
| author_role |
author |
| author2 |
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. |
| author2_role |
author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
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. |
| dc.subject.other.pt_BR.fl_str_mv |
Trypanosoma cruzi Doença de Chagas Tratamento Cardiomiopatias Infecção |
| topic |
Trypanosoma cruzi Doença de Chagas Tratamento Cardiomiopatias Infecção Trypanosoma cruzi Chagas Disease Treatment Cardiomiopathy Infection |
| dc.subject.en.pt_BR.fl_str_mv |
Trypanosoma cruzi Chagas Disease Treatment Cardiomiopathy Infection |
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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. |
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2017 |
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2017 |
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2018-02-08T10:38:50Z |
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2018-02-08T10:38:50Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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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. |
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https://www.arca.fiocruz.br/handle/icict/24755 |
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1935-2727 |
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10.1371/journal.pntd.0006132 |
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1935-2735 |
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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. 1935-2727 10.1371/journal.pntd.0006132 1935-2735 |
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