Chagas disease (CD) is an infection caused by the protozoan Trypanosoma cruzi. It is classified by the World Health Organization as one of the most neglected tropical diseases in the world, and approximately 6 to 7 million people worldwide are believed to be infected with T. cruzi. In addition, it is estimated that less than 1% of patients with CD receive antiparasitic treatment, which is performed using two nitroheterocyclic drugs introduced more than half a century ago, benznidazole and nifurtimox. Both drugs are effective when administered in the acute phase of CD and do not show significant activity in the chronic phase. However, these two drugs have adverse effects and can be long-term treatments. Since it is a disease that primarily affects populations living in pockets of poverty, there is no interest on the part of large pharmaceutical companies in developing research seeking to find drugs with greater efficacy and less toxicity. In other words, there is humanitarian demand, but there is no market. The use of natural products (NPs), especially those of plant origin, is of great importance and contributes to the discovery and development of new drugs. Faced with the diversity observed in NPs, one class of substances stands out: quinones. Lapachol and β-lapachone are two naphthoquinones widely reported in the literature and have attracted great attention in research on quinone chemistry and pharmacology. Lapachol is found as a constituent of several plants, and its occurrence is higher in the Bignoniaceae family, particularly in the genus Tabebuia. In Brazil, Tabebuia species are popularly known as ipê or pau d'arco. β-lapachone can be treated by isomerizing lapachol in the presence of concentrated sulfuric acid. Obtaining compounds derived from β-lapachone has also been widely explored for the synthesis of new compounds with trypanocidal activity, with naphthoimidazole derivatives being the most promising. Until the moment of elaboration of the mentioned project, according to the literature, 6,6-dimethyl-2-(p-toluyl)-3,4,5,6-tetrahydrobenzo[7,8]chromene[5,6-d] imidazole, obtained by the condensation reaction between β-lapachone, ammonia and 4-methylbenzaldehyde, is naphthoimidazole, derived from β-lapachone, which showed greater activity against T. cruzi and, for this reason, was chosen to undergo group approvals pharmacophores of commercial drugs with known antiparasitic activity, such as benznidazole and metronidazole, using a molecular hybridization strategy through copper (I)-catalyzed alkyne-azide cycloaddition reaction (CuAAC). In our planning, we will vary the position of the nitro group present in the imidazole centers, seeking to investigate the relationship of the different risks of reduction of each species of 2-, 4- and 5-nitroimidazole and to relate it to the observed activities against parasite cells, since the reduction potential of each nitroimidazole species changes according to the position of the nitro group in the ring. The results obtained in this work validated the molecular design used, generating improved hybrid molecules that were active against T. cruzi and had a higher selectivity index (lower toxicity against host cells).