2. Academic Validation
  3. Synthesis, trypanocidal activity and docking studies of novel quinoxaline-N-acylhydrazones, designed as cruzain inhibitors candidates

Synthesis, trypanocidal activity and docking studies of novel quinoxaline-N-acylhydrazones, designed as cruzain inhibitors candidates

  • Bioorg Med Chem. 2009 Jan 15;17(2):641-52. doi: 10.1016/j.bmc.2008.11.065.
Nelilma C Romeiro 1,  Gabriela Aguirre,  Paola Hernández,  Mercedes González,  Hugo Cerecetto,  Ignacio Aldana,  Silvia Pérez-Silanes,  Antonio Monge,  Eliezer J Barreiro,  Lídia M Lima
Affiliations

Affiliation

  • 1 Laboratório de Avaliação e Síntese de Substâncias Bioativas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, PO Box 68024, RJ 21944-970, Brazil.
PMID: 19110434 DOI: 10.1016/j.bmc.2008.11.065
Abstract

In this paper, we report the structural design, synthesis, trypanocidal activity and docking studies of novel quinoxaline-N-acylhydrazone (NAH) derivatives, planned as cruzain inhibitors candidates, a cysteine protease essential for the survival of Trypanosoma cruzi within the host cell. The salicylaldehyde N-acylhydrazones 7a and 8a presented IC(50) values of the same magnitude order than the standard drug nifurtimox (Nfx), when tested in vitro against epimastigote forms of Trypanosoma cruzi (Tulahuen 2 strain) and were non-toxic at the highest assayed doses rendering selectivity indexes (IC(50) (macrophages)/IC(50) (Trypanosoma cruzi)) of >25 for 7a and >20 for 8a, with IC(50) values in macrophages >400 microM.

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