However, with chronic stage infections, treatment failures are frequently reported, with noncurative outcomes varying between 6% and 50% in recent clinical trials. As the disease progresses, treatment efficacy decreases. These two redox-active nitroheterocyclic agents are bio-activated through T. cruzi nitroreductase. Additionally, Bz metabolism can cause dermatological, gastrointestinal and nervous system side effects that lead to treatment interruption. While Bz treatment is often associated with relapses and can have side effects, it is considered as more efficacious in the acute phase when parasites are circulating but this asymptomatic phase is difficult to diagnose. Furthermore, Bz metabolites can be highly mutagenic in T. cruzi and promote the selection of multi-drug resistance (against other drugs). Should the disease not be detected or not successfully treated in its early stage; the challenge of the symptomatic stage is even more dauntingfighting the parasite in addition to controlling the inflammation-triggering disorder. Additionally, drug development is challenged by the wide genetic diversity of T. cruzi strains throughout Latin America. Ideally, anti-Chagas drugs acting against the first stage of the disease should be fast-acting and produce mimimal toxicity and secondary effects (). This remains a serious problem with both Bz and Nx. For several decades, compounds inducing oxidative stress have been excluded from drug development, irrespective of the target disease. Observations with simple and non-specific redox-active scaffolds led to a view that pan-assay interference compounds (PAINS) were inappropriate. Consequently, promising reactive oxygen species (ROS)-inducing agents could never be practically exploited.