Studies of genotoxicity and mutagenicity of nitroimidazoles: demystifying this critical relationship with the nitro group

Detalhes bibliográficos
Autor(a) principal: Boechat, Núbia
Data de Publicação: 2015
Outros Autores: Carvalho, Alcione Silva de, Salomão, Kelly, Castro, Solange Lisboa de, Lima, Carlos Fernando Araújo, Mello, Francisco do Vale Chaves e, Felzenszwalb, Israel, Aiub, Claudia Alessandra Fortes, Conde, Taline Ramos, Zamith, Helena Pereira da Silva, Skupin, Rolf, Haufe, Günter
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/11059
http://dx.doi.org/10.1590/0074-02760140248
Resumo: Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Departamento de Síntese de Fármacos. Rio de Janeiro, RJ, Brasil.
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spelling Boechat, NúbiaCarvalho, Alcione Silva deSalomão, KellyCastro, Solange Lisboa deLima, Carlos Fernando AraújoMello, Francisco do Vale Chaves eFelzenszwalb, IsraelAiub, Claudia Alessandra FortesConde, Taline RamosZamith, Helena Pereira da SilvaSkupin, RolfHaufe, Günter2015-07-02T18:52:16Z2015-07-02T18:52:16Z2015BOECHAT, N. et. al. Studies of genotoxicity and mutagenicity of nitroimidazoles: demystifying this critical relationship with the nitro group. Mem. Inst. Oswaldo Cruz, Rio de Janeiro, v. 110, n. 4, p. 492-499, 2015.0074-0276https://www.arca.fiocruz.br/handle/icict/11059http://dx.doi.org/10.1590/0074-02760140248engInstituto Oswaldo CruzNitroimidazóisGenotoxicidadeMutagenicidadeTripanossomicidasNitroimidazolesGenotoxicityMutagenicityTrypanocidal activityNitroimidazóisGenotoxicidadeTestes de MutagenicidadeTripanossomicidasStudies of genotoxicity and mutagenicity of nitroimidazoles: demystifying this critical relationship with the nitro groupinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Departamento de Síntese de Fármacos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Departamento de Síntese de Fármacos. 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. 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 do Estado do Rio de Janeiro. Departamento de Biofísica e Biometria. Rio de Janeiro, RJ, Brasil.Universidade Federal do Estado do Rio de Janeiro. Departamento de Genética e Biologia Molecular. Rio de Janeiro, RJ, Brasil.Universidade Federal do Estado do Rio de Janeiro. Departamento de Genética e Biologia Molecular. Rio de Janeiro, RJ, Brasil.Westfälischen Wilhelms-Universität Münster. Organisch-Chemisches Institut. Münster, Germany.Westfälischen Wilhelms-Universität Münster. Organisch-Chemisches Institut. Münster, Germany.Nitroimidazoles exhibit high microbicidal activity, but mutagenic, genotoxic and cytotoxic properties have been attributed to the presence of the nitro group. However, we synthesised nitroimidazoles with activity against the trypomastigotes of Trypanosoma cruzi, but that were not genotoxic. Herein, nitroimidazoles (11-19) bearing different substituent groups were investigated for their potential induction of genotoxicity (comet assay) and mutagenicity (Salmonella/Microsome assay) and the correlations of these effects with their trypanocidal effect and with megazol were investigated. The compounds were designed to analyse the role played by the position of the nitro group in the imidazole nucleus (C-4 or C-5) and the presence of oxidisable groups at N-1 as an anion receptor group and the role of a methyl group at C-2. Nitroimidazoles bearing NO2 at C-4 and CH3 at C-2 were not genotoxic compared to those bearing NO 2 at C-5. However, when there was a CH3 at C-2, the position of the NO2 group had no influence on the genotoxic activity. Fluorinated compounds exhibited higher genotoxicity regardless of the presence of CH3 at C-2 or NO2 at C-4 or C-5. However, in compounds 11 (2-CH3; 4-NO2; N-CH2OHCH2Cl) and 12 (2-CH3; 4-NO2; N-CH2OHCH2F), the fluorine atom had no influence on genotoxicity. This study contributes to the future search for new and safer prototypes and provide.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82354https://www.arca.fiocruz.br/bitstream/icict/11059/1/license.txt8b4c200b4e10021c5683c6ccaba07169MD51ORIGINALMem_Inst_Oswaldo_Cruz_110_492-499.pdfMem_Inst_Oswaldo_Cruz_110_492-499.pdfapplication/pdf731403https://www.arca.fiocruz.br/bitstream/icict/11059/2/Mem_Inst_Oswaldo_Cruz_110_492-499.pdfe3c80a885f8ca653823b2bbdf158f8c5MD52TEXTMem_Inst_Oswaldo_Cruz_110_492-499.pdf.txtMem_Inst_Oswaldo_Cruz_110_492-499.pdf.txtExtracted texttext/plain38784https://www.arca.fiocruz.br/bitstream/icict/11059/3/Mem_Inst_Oswaldo_Cruz_110_492-499.pdf.txt067aa3d7cdef1eaee57f91b155dd5d44MD53icict/110592018-04-04 08:06:18.766oai:www.arca.fiocruz.br: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Repositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352018-04-04T11:06:18Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv Studies of genotoxicity and mutagenicity of nitroimidazoles: demystifying this critical relationship with the nitro group
title Studies of genotoxicity and mutagenicity of nitroimidazoles: demystifying this critical relationship with the nitro group
spellingShingle Studies of genotoxicity and mutagenicity of nitroimidazoles: demystifying this critical relationship with the nitro group
Boechat, Núbia
Nitroimidazóis
Genotoxicidade
Mutagenicidade
Tripanossomicidas
Nitroimidazoles
Genotoxicity
Mutagenicity
Trypanocidal activity
Nitroimidazóis
Genotoxicidade
Testes de Mutagenicidade
Tripanossomicidas
title_short Studies of genotoxicity and mutagenicity of nitroimidazoles: demystifying this critical relationship with the nitro group
title_full Studies of genotoxicity and mutagenicity of nitroimidazoles: demystifying this critical relationship with the nitro group
title_fullStr Studies of genotoxicity and mutagenicity of nitroimidazoles: demystifying this critical relationship with the nitro group
title_full_unstemmed Studies of genotoxicity and mutagenicity of nitroimidazoles: demystifying this critical relationship with the nitro group
title_sort Studies of genotoxicity and mutagenicity of nitroimidazoles: demystifying this critical relationship with the nitro group
author Boechat, Núbia
author_facet Boechat, Núbia
Carvalho, Alcione Silva de
Salomão, Kelly
Castro, Solange Lisboa de
Lima, Carlos Fernando Araújo
Mello, Francisco do Vale Chaves e
Felzenszwalb, Israel
Aiub, Claudia Alessandra Fortes
Conde, Taline Ramos
Zamith, Helena Pereira da Silva
Skupin, Rolf
Haufe, Günter
author_role author
author2 Carvalho, Alcione Silva de
Salomão, Kelly
Castro, Solange Lisboa de
Lima, Carlos Fernando Araújo
Mello, Francisco do Vale Chaves e
Felzenszwalb, Israel
Aiub, Claudia Alessandra Fortes
Conde, Taline Ramos
Zamith, Helena Pereira da Silva
Skupin, Rolf
Haufe, Günter
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Boechat, Núbia
Carvalho, Alcione Silva de
Salomão, Kelly
Castro, Solange Lisboa de
Lima, Carlos Fernando Araújo
Mello, Francisco do Vale Chaves e
Felzenszwalb, Israel
Aiub, Claudia Alessandra Fortes
Conde, Taline Ramos
Zamith, Helena Pereira da Silva
Skupin, Rolf
Haufe, Günter
dc.subject.other.pt_BR.fl_str_mv Nitroimidazóis
Genotoxicidade
Mutagenicidade
Tripanossomicidas
topic Nitroimidazóis
Genotoxicidade
Mutagenicidade
Tripanossomicidas
Nitroimidazoles
Genotoxicity
Mutagenicity
Trypanocidal activity
Nitroimidazóis
Genotoxicidade
Testes de Mutagenicidade
Tripanossomicidas
dc.subject.en.pt_BR.fl_str_mv Nitroimidazoles
Genotoxicity
Mutagenicity
Trypanocidal activity
dc.subject.decs.pt_BR.fl_str_mv Nitroimidazóis
Genotoxicidade
Testes de Mutagenicidade
Tripanossomicidas
description Fundação Oswaldo Cruz. Instituto de Tecnologia em Fármacos. Departamento de Síntese de Fármacos. Rio de Janeiro, RJ, Brasil.
publishDate 2015
dc.date.accessioned.fl_str_mv 2015-07-02T18:52:16Z
dc.date.available.fl_str_mv 2015-07-02T18:52:16Z
dc.date.issued.fl_str_mv 2015
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 BOECHAT, N. et. al. Studies of genotoxicity and mutagenicity of nitroimidazoles: demystifying this critical relationship with the nitro group. Mem. Inst. Oswaldo Cruz, Rio de Janeiro, v. 110, n. 4, p. 492-499, 2015.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/11059
dc.identifier.issn.none.fl_str_mv 0074-0276
dc.identifier.doi.none.fl_str_mv http://dx.doi.org/10.1590/0074-02760140248
identifier_str_mv BOECHAT, N. et. al. Studies of genotoxicity and mutagenicity of nitroimidazoles: demystifying this critical relationship with the nitro group. Mem. Inst. Oswaldo Cruz, Rio de Janeiro, v. 110, n. 4, p. 492-499, 2015.
0074-0276
url https://www.arca.fiocruz.br/handle/icict/11059
http://dx.doi.org/10.1590/0074-02760140248
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 Instituto Oswaldo Cruz
publisher.none.fl_str_mv Instituto Oswaldo Cruz
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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