Antitrypanosomal Activity of Sterol 14α-Demethylase (CYP51) Inhibitors VNI and VFV in the Swiss Mouse Models of Chagas Disease Induced by the Trypanosoma cruzi Y Strain

Detalhes bibliográficos
Autor(a) principal: Batista, D. G. J.
Data de Publicação: 2017
Outros Autores: Silva, C. F. da, Araújo, J. S. de, Pavão, B. P., Silva, M. R. Simões, Batista, M. M., Demarque, K. C., Moreira, O. C., Britto, C., Lepesheva, G. I., Soeiro, M. N. C.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/19672
Resumo: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ. Brasil.
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spelling Batista, D. G. J.Silva, C. F. daAraújo, J. S. dePavão, B. P.Silva, M. R. SimõesBatista, M. M.Demarque, K. C.Moreira, O. C.Britto, C.Lepesheva, G. I.Soeiro, M. N. C.2017-06-29T15:16:48Z2017-06-29T15:16:48Z2017SILVA, F. H. Guedes da; et al. Antitrypanosomal Activity of Sterol 14 - Demethylase (CYP51) Inhibitors VNI and VFV in the Swiss Mouse Models of Chagas Disease Induced by the Trypanosoma cruzi Y Strain. Antimicrobial Agents and Chemotherapy, v.61, n.4, e02098-16, 9p, Apr. 2017.0066-4804https://www.arca.fiocruz.br/handle/icict/1967210.1128/AAC.02098-161098-6596engAmerican Society for MicrobiologyDoença de ChagasQuimioterapiaTrypanosoma cruziInibidoresChagas Diseasechemotherapysterol 14 -demethylaseinhibitorsVNIVNFTrypanosoma cruziAntitrypanosomal Activity of Sterol 14α-Demethylase (CYP51) Inhibitors VNI and VFV in the Swiss Mouse Models of Chagas Disease Induced by the Trypanosoma cruzi Y Straininfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ. Brasil.undação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ. Brasil.Vanderbilt University. Institute for Global Health. School of Medicine. Department of Biochemistry. Nashville, Tennessee, USA.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ. Brasil.Chagas disease is a life-threatening infection caused by a variety of genetically diverse strains of the protozoan parasite Trypanosoma cruzi The current treatment (benznidazole and nifurtimox) is unsatisfactory, and potential alternatives include inhibitors of sterol 14α-demethylase (CYP51), the cytochrome P450 enzyme essential for the biosynthesis of sterols in eukaryotes and the major target of clinical and agricultural antifungals. Here we performed a comparative investigation of two protozoon-specific CYP51 inhibitors, VNI and its CYP51 structure-based derivative VFV, in the murine models of infection caused by the Y strain of T. cruzi The effects of different treatment regimens and drug delivery vehicles were evaluated in animals of both genders, with benznidazole serving as the reference drug. Regardless of the treatment scheme or delivery vehicle, VFV was more potent in both genders, causing a >99.7% peak parasitemia reduction, while the VNI values varied from 91 to 100%. Treatments with VNI and VFV resulted in 100% animal survival and 0% natural relapse after the end of therapy, though, except for the 120-day treatment schemes with VFV, relapses after three cycles of immunosuppression were observed in each animal group, and quantitative PCR analysis revealed a very light parasite load in the blood samples (sometimes below or near the detection limit, which was 1.5 parasite equivalents/ml). Our studies support further investigations of this class of compounds, including their testing against other T. cruzi strains and in combination with other drugs.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/19672/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALfhguedes_dasilva_etal_IOC_2017.pdffhguedes_dasilva_etal_IOC_2017.pdfapplication/pdf966811https://www.arca.fiocruz.br/bitstream/icict/19672/2/fhguedes_dasilva_etal_IOC_2017.pdff5ca760081290e10234a6eb937494d09MD52TEXTfhguedes_dasilva_etal_IOC_2017.pdf.txtfhguedes_dasilva_etal_IOC_2017.pdf.txtExtracted texttext/plain40266https://www.arca.fiocruz.br/bitstream/icict/19672/3/fhguedes_dasilva_etal_IOC_2017.pdf.txtaf90626e46fdc06a15e9c6834d63fd5aMD53icict/196722018-08-15 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dc.title.pt_BR.fl_str_mv Antitrypanosomal Activity of Sterol 14α-Demethylase (CYP51) Inhibitors VNI and VFV in the Swiss Mouse Models of Chagas Disease Induced by the Trypanosoma cruzi Y Strain
title Antitrypanosomal Activity of Sterol 14α-Demethylase (CYP51) Inhibitors VNI and VFV in the Swiss Mouse Models of Chagas Disease Induced by the Trypanosoma cruzi Y Strain
spellingShingle Antitrypanosomal Activity of Sterol 14α-Demethylase (CYP51) Inhibitors VNI and VFV in the Swiss Mouse Models of Chagas Disease Induced by the Trypanosoma cruzi Y Strain
Batista, D. G. J.
Doença de Chagas
Quimioterapia
Trypanosoma cruzi
Inibidores
Chagas Disease
chemotherapy
sterol 14 -demethylase
inhibitors
VNI
VNF
Trypanosoma cruzi
title_short Antitrypanosomal Activity of Sterol 14α-Demethylase (CYP51) Inhibitors VNI and VFV in the Swiss Mouse Models of Chagas Disease Induced by the Trypanosoma cruzi Y Strain
title_full Antitrypanosomal Activity of Sterol 14α-Demethylase (CYP51) Inhibitors VNI and VFV in the Swiss Mouse Models of Chagas Disease Induced by the Trypanosoma cruzi Y Strain
title_fullStr Antitrypanosomal Activity of Sterol 14α-Demethylase (CYP51) Inhibitors VNI and VFV in the Swiss Mouse Models of Chagas Disease Induced by the Trypanosoma cruzi Y Strain
title_full_unstemmed Antitrypanosomal Activity of Sterol 14α-Demethylase (CYP51) Inhibitors VNI and VFV in the Swiss Mouse Models of Chagas Disease Induced by the Trypanosoma cruzi Y Strain
title_sort Antitrypanosomal Activity of Sterol 14α-Demethylase (CYP51) Inhibitors VNI and VFV in the Swiss Mouse Models of Chagas Disease Induced by the Trypanosoma cruzi Y Strain
author Batista, D. G. J.
author_facet Batista, D. G. J.
Silva, C. F. da
Araújo, J. S. de
Pavão, B. P.
Silva, M. R. Simões
Batista, M. M.
Demarque, K. C.
Moreira, O. C.
Britto, C.
Lepesheva, G. I.
Soeiro, M. N. C.
author_role author
author2 Silva, C. F. da
Araújo, J. S. de
Pavão, B. P.
Silva, M. R. Simões
Batista, M. M.
Demarque, K. C.
Moreira, O. C.
Britto, C.
Lepesheva, G. I.
Soeiro, M. N. C.
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Batista, D. G. J.
Silva, C. F. da
Araújo, J. S. de
Pavão, B. P.
Silva, M. R. Simões
Batista, M. M.
Demarque, K. C.
Moreira, O. C.
Britto, C.
Lepesheva, G. I.
Soeiro, M. N. C.
dc.subject.other.pt_BR.fl_str_mv Doença de Chagas
Quimioterapia
Trypanosoma cruzi
Inibidores
topic Doença de Chagas
Quimioterapia
Trypanosoma cruzi
Inibidores
Chagas Disease
chemotherapy
sterol 14 -demethylase
inhibitors
VNI
VNF
Trypanosoma cruzi
dc.subject.en.pt_BR.fl_str_mv Chagas Disease
chemotherapy
sterol 14 -demethylase
inhibitors
VNI
VNF
Trypanosoma cruzi
description Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ. Brasil.
publishDate 2017
dc.date.accessioned.fl_str_mv 2017-06-29T15:16:48Z
dc.date.available.fl_str_mv 2017-06-29T15:16:48Z
dc.date.issued.fl_str_mv 2017
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv SILVA, F. H. Guedes da; et al. Antitrypanosomal Activity of Sterol 14 - Demethylase (CYP51) Inhibitors VNI and VFV in the Swiss Mouse Models of Chagas Disease Induced by the Trypanosoma cruzi Y Strain. Antimicrobial Agents and Chemotherapy, v.61, n.4, e02098-16, 9p, Apr. 2017.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/19672
dc.identifier.issn.pt_BR.fl_str_mv 0066-4804
dc.identifier.doi.none.fl_str_mv 10.1128/AAC.02098-16
dc.identifier.eissn.none.fl_str_mv 1098-6596
identifier_str_mv SILVA, F. H. Guedes da; et al. Antitrypanosomal Activity of Sterol 14 - Demethylase (CYP51) Inhibitors VNI and VFV in the Swiss Mouse Models of Chagas Disease Induced by the Trypanosoma cruzi Y Strain. Antimicrobial Agents and Chemotherapy, v.61, n.4, e02098-16, 9p, Apr. 2017.
0066-4804
10.1128/AAC.02098-16
1098-6596
url https://www.arca.fiocruz.br/handle/icict/19672
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
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