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 NO
2 at C-4 and CH
3 at C-2 were not genotoxic compared to those bearing NO
2 at C-5. However,
when there was a CH
3 at C-2, the position of the NO
2 group had no influence on the genotoxic activity. Fluorinated
compounds exhibited higher genotoxicity regardless of the presence of CH
3 at C-2 or NO
2 at C-4 or C-5. However, in
compounds 11 (2-CH
3; 4-NO
2; N-CH
2OHCH
2Cl) and 12 (2-CH
3; 4-NO
2; N-CH
2OHCH
2F), the fluorine atom had no
influence on genotoxicity. This study contributes to the future search for new and safer prototypes and provide.
