Abstract

Background: The drugs available for the treatment of Chagas disease are ineffective in its chronic phase and produce many adverse effects, making the search for new drugs an urgent medical need.

Objective: This study aimed to design, synthesize, and evaluate the trypanocidal and cytotoxic profiles of new 4-nitroimidazole prototypes.

Methods: The new compounds were synthesized in overall yields ranging from 31-to 52% through the use of classical and reproducible methodologies. Their trypanocidal profile and cytotoxicity were assayed against trypomastigote forms of T. cruzi and mammalian macrophages, respectively.

Results: The best trypanocidal activity was evidenced in compounds that present lipophilic and electronegative substituents, e.g. 4-chlorophenyl derivative (5), with an IC₅₀ = 206.98 μM;

Conclusion: The new benznidazole N-glycinyl-hydrazone analogues demonstrated a very significant reduction in the trypanocidal activity compared to benznidazole, which seems to be related to the position occupied by the nitro group in the imidazole ring.

Keywords: Trypanocidal activity, chagas disease, Trypanosoma cruzi, hydrazones, 4-nitroimidazoles, acylhydrazones.

Graphical Abstract