AI Article Synopsis
- The study aimed to identify how nitro-group compounds, potential drug leads for Chagas' disease, target the parasite Trypanosoma cruzi.
- Nine nitrofurans and nitroimidazoles were examined for their efficacy, redox cycling ability, respiratory inhibition, and production of nitroso derivatives.
- Results showed that nifurtimox acts as a redox cycler, while the 5-nitroimidazole megazol is particularly effective as a thiol scavenger targeting trypanothione, crucial for detoxification.
Article Abstract
With the aim of determining the actual target(s) of nitro-group bearing compounds considered as possible leads for the development of drugs against Chagas' disease, we studied in parallel nitrofurans and nitroimidazoles. We investigated nine representative compounds for the following properties: efficacy on different Trypanosoma cruzi strains, redox cyclers, inhibition of respiration, production of corresponding nitroso derivatives and intracellular thiol scavengers. Our results indicate that nifurtimox and related compounds act as redox cyclers, whereas the most active in the series, the 5-nitroimidazole megazol essentially acts as thiol scavenger particularly for trypanothione, the cofactor for trypanothione reductase, an essential enzyme in the detoxification process.
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| http://dx.doi.org/10.1016/s0006-2952(02)01663-5 | DOI Listing |
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