In vitro genotoxicity of nitroimidazoles as a tool in the search of new trypanocidal agents

Detalhes bibliográficos
Autor(a) principal: Von Trompowsky, Ana Claudia Manuel
Data de Publicação: 2019
Outros Autores: Conde, Taline Ramos, Lemos, Renata Calil, Quaresma, Bruna Maria C. S., Pitombeira, Marcelly Cristina S. R., Carvalho, Alcione Silva de, Boechat, Núbia, Salomão, Kelly, Castro, Solange Lisboa de, Zamith, Helena Pereira da Silva
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/35333
Resumo: Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde. Departamento de Farmacologia e Toxicologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde. Programa de Pós-Graduação em Vigilância Sanitária. Rio de Janeiro, RJ, Brasil.
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spelling Von Trompowsky, Ana Claudia ManuelConde, Taline RamosLemos, Renata CalilQuaresma, Bruna Maria C. S.Pitombeira, Marcelly Cristina S. R.Carvalho, Alcione Silva deBoechat, NúbiaSalomão, KellyCastro, Solange Lisboa deZamith, Helena Pereira da Silva2019-09-04T14:15:45Z2019-09-04T14:15:45Z2019VON TROMPOWSKY, Ana Claudia Manoel et al. In vitro genotoxicity of nitroimidazoles as a tool in the search of new trypanocidal agents. Memórias do Instituto Oswaldo Cruz, Rio de Janeiro, v. 114, p. 1-10, 2019.0074-0276https://www.arca.fiocruz.br/handle/icict/3533310.1590/0074-027601900171678-8060engFundação Oswaldo Cruz. Instituto Oswaldo Cruz.GenotoxicidadeMutagenicidadeMegazolNitroimidazóisGenotoxicityMutagenicityMegazolNitroimidazolesIn vitro genotoxicity of nitroimidazoles as a tool in the search of new trypanocidal agentsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde. Departamento de Farmacologia e Toxicologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde. Programa de Pós-Graduação em Vigilância Sanitária. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde. Departamento de Farmacologia e Toxicologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde. Departamento de Farmacologia e Toxicologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Programa de Pós-Graduação em Farmacologia e Química Medicinal. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas. Programa de Pós-Graduação em Farmacologia e Química Medicinal. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Departamento de Síntese de Fármacos. Farmanguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Departamento de Síntese de Fármacos. Farmanguinhos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Departamento de Síntese de Fármacos. Farmanguinhos. 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 Nacional de Controle de Qualidade em Saúde. Departamento de Farmacologia e Toxicologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde. Programa de Pós-Graduação em Vigilância Sanitária. Rio de Janeiro, RJ, Brasil.Only benznidazole (Bnz) (1) and nifurtimox (Nfx) (2) are licensed for the treatment of Chagas disease although their safety and efficacy profile are far from ideal. Farmanguinhos from Fiocruz has developed seven nitroimidazole compounds (4-10) analogs of megazol (3). OBJECTIVES To evaluate whether the genotoxic effect of 3 was abolished in the seven nitroimidazoles (4-10) analogs using the in vitro alkaline comet assay (CA) and the in vitro cytokinesis-block micronucleus assay (CBMN) in whole human blood cells (WHBC) and correlate this effect with their trypanocidal activity using bloodstream trypomastigote forms of Trypanosoma cruzi. METHODS The toxicity of 3-10 to WHBC in the in vitro CA was determined using the fluorescein diacetate/ethidium bromide assay. DNA damage in the in vitro CA was evaluated according to tail size in four classes (0-3) and methyl methane-sulfonate (MMS) was used as a positive control. The cytotoxicity of 3-10 to WHBC in the CBMN was measured using the cytokinesis-block proliferation index and the replication index. The number of the micronucleate cells in 2,000 binucleate cells by experimental group was determined. Mitomycin C and N-deacetyl-N-methylcolchicine were used as positive controls. FINDINGS Compound 3 showed a significant DNA strand break effect through the in vitro CA and highly significant clastogenic and/or aneugenic effect in the CBMN. Compounds 5, 6, 8, 9 and 10 showed negative results in the CBMN and positive results in the in vitro CA, while the inverse effect was observed for 4 and 7. MAIN CONCLUSIONS Compound 10 was the most promising to proceed with the development as a drug candidate in the treatment of Chagas disease showing absence of chromosomal cytogenetic damage and high activity against T. cruzi, about two times higher than 3 and the clinical drug 1.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/35333/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALKellySalomao_SolangeCastro_etal_IOC_2019.pdfKellySalomao_SolangeCastro_etal_IOC_2019.pdfapplication/pdf731304https://www.arca.fiocruz.br/bitstream/icict/35333/2/KellySalomao_SolangeCastro_etal_IOC_2019.pdfadf3685bf6509cf92b26ed34e0f568e0MD52TEXTKellySalomao_SolangeCastro_etal_IOC_2019.pdf.txtKellySalomao_SolangeCastro_etal_IOC_2019.pdf.txtExtracted 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dc.title.pt_BR.fl_str_mv In vitro genotoxicity of nitroimidazoles as a tool in the search of new trypanocidal agents
title In vitro genotoxicity of nitroimidazoles as a tool in the search of new trypanocidal agents
spellingShingle In vitro genotoxicity of nitroimidazoles as a tool in the search of new trypanocidal agents
Von Trompowsky, Ana Claudia Manuel
Genotoxicidade
Mutagenicidade
Megazol
Nitroimidazóis
Genotoxicity
Mutagenicity
Megazol
Nitroimidazoles
title_short In vitro genotoxicity of nitroimidazoles as a tool in the search of new trypanocidal agents
title_full In vitro genotoxicity of nitroimidazoles as a tool in the search of new trypanocidal agents
title_fullStr In vitro genotoxicity of nitroimidazoles as a tool in the search of new trypanocidal agents
title_full_unstemmed In vitro genotoxicity of nitroimidazoles as a tool in the search of new trypanocidal agents
title_sort In vitro genotoxicity of nitroimidazoles as a tool in the search of new trypanocidal agents
author Von Trompowsky, Ana Claudia Manuel
author_facet Von Trompowsky, Ana Claudia Manuel
Conde, Taline Ramos
Lemos, Renata Calil
Quaresma, Bruna Maria C. S.
Pitombeira, Marcelly Cristina S. R.
Carvalho, Alcione Silva de
Boechat, Núbia
Salomão, Kelly
Castro, Solange Lisboa de
Zamith, Helena Pereira da Silva
author_role author
author2 Conde, Taline Ramos
Lemos, Renata Calil
Quaresma, Bruna Maria C. S.
Pitombeira, Marcelly Cristina S. R.
Carvalho, Alcione Silva de
Boechat, Núbia
Salomão, Kelly
Castro, Solange Lisboa de
Zamith, Helena Pereira da Silva
author2_role author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Von Trompowsky, Ana Claudia Manuel
Conde, Taline Ramos
Lemos, Renata Calil
Quaresma, Bruna Maria C. S.
Pitombeira, Marcelly Cristina S. R.
Carvalho, Alcione Silva de
Boechat, Núbia
Salomão, Kelly
Castro, Solange Lisboa de
Zamith, Helena Pereira da Silva
dc.subject.other.pt_BR.fl_str_mv Genotoxicidade
Mutagenicidade
Megazol
Nitroimidazóis
topic Genotoxicidade
Mutagenicidade
Megazol
Nitroimidazóis
Genotoxicity
Mutagenicity
Megazol
Nitroimidazoles
dc.subject.en.pt_BR.fl_str_mv Genotoxicity
Mutagenicity
Megazol
Nitroimidazoles
description Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde. Departamento de Farmacologia e Toxicologia. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde. Programa de Pós-Graduação em Vigilância Sanitária. Rio de Janeiro, RJ, Brasil.
publishDate 2019
dc.date.accessioned.fl_str_mv 2019-09-04T14:15:45Z
dc.date.available.fl_str_mv 2019-09-04T14:15:45Z
dc.date.issued.fl_str_mv 2019
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 VON TROMPOWSKY, Ana Claudia Manoel et al. In vitro genotoxicity of nitroimidazoles as a tool in the search of new trypanocidal agents. Memórias do Instituto Oswaldo Cruz, Rio de Janeiro, v. 114, p. 1-10, 2019.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/35333
dc.identifier.issn.pt_BR.fl_str_mv 0074-0276
dc.identifier.doi.none.fl_str_mv 10.1590/0074-02760190017
dc.identifier.eissn.none.fl_str_mv 1678-8060
identifier_str_mv VON TROMPOWSKY, Ana Claudia Manoel et al. In vitro genotoxicity of nitroimidazoles as a tool in the search of new trypanocidal agents. Memórias do Instituto Oswaldo Cruz, Rio de Janeiro, v. 114, p. 1-10, 2019.
0074-0276
10.1590/0074-02760190017
1678-8060
url https://www.arca.fiocruz.br/handle/icict/35333
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 Fundação Oswaldo Cruz. Instituto Oswaldo Cruz.
publisher.none.fl_str_mv Fundação Oswaldo Cruz. Instituto Oswaldo Cruz.
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
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collection Repositório Institucional da FIOCRUZ (ARCA)
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https://www.arca.fiocruz.br/bitstream/icict/35333/2/KellySalomao_SolangeCastro_etal_IOC_2019.pdf
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