Title:New 4-nitro-imidazole-N-glycinyl-hydrazones Designed as Trypanocidal
Analogues of Benznidazole
Volume: 20
Issue: 4
Author(s): Giulianna P. de Alcântara, Juliana M.C. Barbosa, Kelly Salomão, Solange L. de Castro, James L. Wardell, John N. Low, Solange M.S.V. Wardell, Samir A. Carvalho, Edson F. da Silva and Carlos A.M. Fraga*
Affiliation:
- Laboratório de Avaliação e Síntese de
Substâncias Bioativas (LASSBio), Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, 21941-
902, Rio de Janeiro, RJ, Brazil
Keywords:
Trypanocidal activity, chagas disease, Trypanosoma cruzi, hydrazones, 4-nitroimidazoles, acylhydrazones.
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.
