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

dc.creatorBoechat, Núbia
dc.creatorCarvalho, Alcione Silva de
dc.creatorSalomão, Kelly
dc.creatorCastro, Solange Lisboa de
dc.creatorLima, Carlos Fernando Araújo
dc.creatorMello, Francisco do Vale Chaves e
dc.creatorFelzenszwalb, Israel
dc.creatorAiub, Claudia Alessandra Fortes
dc.creatorConde, Taline Ramos
dc.creatorZamith, Helena Pereira da Silva
dc.creatorSkupin, Rolf
dc.creatorHaufe, Günter
dc.date2015-07-02T18:52:16Z
dc.date2015-07-02T18:52:16Z
dc.date2015
dc.date.accessioned2023-09-26T22:30:33Z
dc.date.available2023-09-26T22:30:33Z
dc.identifierBOECHAT, 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.identifier0074-0276
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/11059
dc.identifierhttp://dx.doi.org/10.1590/0074-02760140248
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8880137
dc.descriptionNitroimidazoles 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherInstituto Oswaldo Cruz
dc.rightsopen access
dc.subjectNitroimidazóis
dc.subjectGenotoxicidade
dc.subjectMutagenicidade
dc.subjectTripanossomicidas
dc.subjectNitroimidazoles
dc.subjectGenotoxicity
dc.subjectMutagenicity
dc.subjectTrypanocidal activity
dc.subjectNitroimidazóis
dc.subjectGenotoxicidade
dc.subjectTestes de Mutagenicidade
dc.subjectTripanossomicidas
dc.titleStudies of genotoxicity and mutagenicity of nitroimidazoles: demystifying this critical relationship with the nitro group
dc.typeArticle


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