title: Synthesis, trypanocidal activity and docking studies of novel quinoxaline-N-acylhydrazones, designed as cruzain inhibitors candidates.
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.
authors.affiliation: 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.
authors.forename: Nelilma C
authors.initials: NC
authors.lastname: Romeiro
authors.forename: Gabriela
authors.initials: G
authors.lastname: Aguirre
authors.forename: Paola
authors.initials: P
authors.lastname: Hernández
authors.forename: Mercedes
authors.initials: M
authors.lastname: González
authors.forename: Hugo
authors.initials: H
authors.lastname: Cerecetto
authors.forename: Ignacio
authors.initials: I
authors.lastname: Aldana
authors.forename: Silvia
authors.initials: S
authors.lastname: Pérez-Silanes
authors.forename: Antonio
authors.initials: A
authors.lastname: Monge
authors.forename: Eliezer J
authors.initials: EJ
authors.lastname: Barreiro
authors.forename: Lídia M
authors.initials: LM
authors.lastname: Lima
mesh_terms: D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis*; D006835:Hydrazones / Q000138:chemical synthesis*; D020128:Inhibitory Concentration 50; D008264:Macrophages / Q000469:parasitology; D051379:Mice; D009547:Nifurtimox; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors*; D011810:Quinoxalines / Q000138:chemical synthesis; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D015853:Cysteine Proteinase Inhibitors; D006835:Hydrazones; D015800:Protozoan Proteins; D011810:Quinoxalines; D014344:Trypanocidal Agents; D003546:Cysteine Endopeptidases; C074032:cruzain, Trypanosoma cruzi; D009547:Nifurtimox