III. Diseño, síntesis y estudio de un compuesto con posible actividad tripanosomicida

During the symposium "Design of new drugs in Mexico", we presented a summary of the research that led us to develop substances with trypanocidal activity. The epidemiological pattern of Chagas' disease was briefly described as well as the factor that explains the low cure rate seen among chagasic patients. The strategy used to develop a new compound with trypanocidal activity was the following: we used T. cruzi a-hydroxiacid dehydrogenase isoenzyme II, as a target enzyme, trying to inhibit the energetic methabolism of this parasite. N-isopropyl oxamic acid the substance we designed was synthesized and its biological activity was determined. It is a selective inhibitor of this enzyme and in addition, showed trypanocidal activity on cultured epimastigotes, circulating trypomastigotes and intracellular amastigotes. Preliminary studies show the trypanocidal effect of the ethyl ester of N-isopropyl oxamic acid on intracellular amastigotes. This compound reduced by 60-80% the number of amastigotes nests on both cardiac and skeletal muscle, whereas Nifurtimox, the currently drug used for treatment of this disease, produced a reduction on amastigotes nests of 20-30%, in agreement with previous reports describing the low trypanocidal effect of this compound, in chronic stages of Chagas' disease.