Oxygen radicals and the chemotherapy of Chagas' disease: an overview

ABSTRACT

Current knowledge on the role of oxygen radicals in the development of chemotherapy for Chagas' disease is reviewed. This includes a) a brief description of the disease and its prevalence in the endemic area; b) applicability and toxicity of nifurtimox and benznidazole; c) the production of oxygen radicals by nitrocompounds, specially by nifurtimox; d) the action of nifurtimox and benzidazole on DNA, RNA and protein synthesis and degradation in Trypanosoma cruzi, including nuclear DNA and kinetoplast DNA cleavage and repair; e) nifurtimox reduction by lipoamide dehydrogenase; J) the role of T cruzi trypanothione system; g) the chemical and biological consequences of replacing the tetrahydrothiazine group of nifurtimox by unsaturated nitrogen heterocycles; h) the electronic properties of the new compounds, in relation to their capability for nitroanion radical production and trypanocidal action in vitro (QSAR) and in vivo; i) evidence for the possible role of oxygen radicals in the action of nifurtimox on T. cruzi and the human host. It is concluded that the chemotherapy of Chagas'disease remains an unsolved problem and, therefore, the search for new drugs must continue.