Background: Approximately, 5-7 million people are infected with T. cruzi in the world, and approximately 10,000 people per year die of complications linked to this disease. Method: This work describes the construction of a new family of hidrazonoyl substituted derivatives, structurally designed exploring the molecular hybridization between megazol and nitrofurazone. Results and Discussion: The compounds were evaluated for their in vitro activity against bloodstream trypomastigotes of Trypanosoma cruzi, etiological agent of Chagas disease, and for their potential toxicity to mammalian cells. Conclusion: Among these hydrazonoyl derivatives, we identified the derivative (4) that showed trypanocidal activity (IC50/24 h = 15.0 µM) similar to Bz, the standard drug, and low toxicity to mammalian cells, reaching an SI value of 18.7.