Mutagenicity assessment of novel nitroimidazooxazole anti-infective candidates using the Ames Test

Nitroimidazole-based compounds are widely explored as anti-infective agents, although their nitro group may be associated with genotoxicity concerns. Here, we investigated the mutagenic profile of ten nitroimidazooxazole derivatives (49–58) previously developed for antimycobacterial and antileishmanial applications. The compounds were evaluated by the Ames test using Salmonella Typhimurium strains TA98, TA97a, TA100, and TA102, with and without metabolic activation by S9. Five concentrations were tested, from 31.25 to 250 μg/plate, using the pre-incubation protocol, with assays performed in triplicate. Mutagenicity was evaluated using revertant colony counts, dose-response trends, statistical comparisons with the negative control, and the mutagenicity index. Across all strains and experimental conditions, none of the compounds produced a significant increase in the number of revertants. The mutagenicity index remained below 2 at every concentration tested, and no consistent concentration-dependent response was observed. The expected responses obtained with the positive controls confirmed the validity of the assays. Taken together, these results show that derivatives 49–58 did not exhibit mutagenic activity in the bacterial reverse mutation assay, regardless of metabolic activation, supporting their continued preclinical evaluation as anti-infective candidates.