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Memórias do Instituto Oswaldo Cruz
Fundação Oswaldo Cruz, Fiocruz
ISSN: 1678-8060
EISSN: 1678-8060
Vol. 110, No. 4, 2015, pp. 492-499
Bioline Code: oc15062
Full paper language: English
Document type: Research Article
Document available free of charge

Memórias do Instituto Oswaldo Cruz, Vol. 110, No. 4, 2015, pp. 492-499

 en Studies of genotoxicity and mutagenicity of nitroimidazoles: demystifying this critical relationship with the nitro group
Boechat, Núbia; Carvalho, Alcione S.; Salomão, Kelly; de Castro, Solange L.; Araujo-Lima, Carlos F.; Mello, Francisco V.C.; Felzenszwalb, Israel; Aiub, Claudia A.F.; Conde, Taline Ramos; Zamith, Helena P.S.; Skupin, Rolf & Haufe, Günter

Abstract

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 check for this species in other resources /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.

Keywords
nitroimidazoles; genotoxicity; mutagenicity; trypanocidal activity

 
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