Studies of genotoxicity and mutagenicity of nitroimidazoles: demystifying this critical relationship with the nitro group
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,...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Fundação Oswaldo Cruz (FIOCRUZ)
2015-06-01
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| Series: | Memorias do Instituto Oswaldo Cruz |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762015000400492&lng=en&tlng=en |
| _version_ | 1827880207755771904 |
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| author | Núbia Boechat Alcione S Carvalho Kelly Salomão Solange L de Castro Carlos F Araujo-Lima Francisco VC Mello Israel Felzenszwalb Claudia AF Aiub Taline Ramos Conde Helena PS Zamith Rolf Skupin Günter Haufe |
| author_facet | Núbia Boechat Alcione S Carvalho Kelly Salomão Solange L de Castro Carlos F Araujo-Lima Francisco VC Mello Israel Felzenszwalb Claudia AF Aiub Taline Ramos Conde Helena PS Zamith Rolf Skupin Günter Haufe |
| author_sort | Núbia Boechat |
| collection | DOAJ |
| description | 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 NO2 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. |
| first_indexed | 2024-03-12T18:18:31Z |
| format | Article |
| id | doaj.art-c1cc5577d9de48da883a1d819514d3ba |
| institution | Directory Open Access Journal |
| issn | 1678-8060 |
| language | English |
| last_indexed | 2024-03-12T18:18:31Z |
| publishDate | 2015-06-01 |
| publisher | Fundação Oswaldo Cruz (FIOCRUZ) |
| record_format | Article |
| series | Memorias do Instituto Oswaldo Cruz |
| spelling | doaj.art-c1cc5577d9de48da883a1d819514d3ba2023-08-02T09:00:09ZengFundação Oswaldo Cruz (FIOCRUZ)Memorias do Instituto Oswaldo Cruz1678-80602015-06-01110449249910.1590/0074-02760140248S0074-02762015000400492Studies of genotoxicity and mutagenicity of nitroimidazoles: demystifying this critical relationship with the nitro groupNúbia BoechatAlcione S CarvalhoKelly SalomãoSolange L de CastroCarlos F Araujo-LimaFrancisco VC MelloIsrael FelzenszwalbClaudia AF AiubTaline Ramos CondeHelena PS ZamithRolf SkupinGünter HaufeNitroimidazoles 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 NO2 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.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762015000400492&lng=en&tlng=ennitroimidazolesgenotoxicitymutagenicitytrypanocidal activity |
| spellingShingle | Núbia Boechat Alcione S Carvalho Kelly Salomão Solange L de Castro Carlos F Araujo-Lima Francisco VC Mello Israel Felzenszwalb Claudia AF Aiub Taline Ramos Conde Helena PS Zamith Rolf Skupin Günter Haufe Studies of genotoxicity and mutagenicity of nitroimidazoles: demystifying this critical relationship with the nitro group Memorias do Instituto Oswaldo Cruz nitroimidazoles genotoxicity mutagenicity trypanocidal activity |
| title | 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_short | 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 |
| topic | nitroimidazoles genotoxicity mutagenicity trypanocidal activity |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762015000400492&lng=en&tlng=en |
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