Synthesis, trypanocidal activity and docking studies of novel quinoxaline-N-acylhydrazones, designed as cruzain inhibitors candidates.
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.
Romeiro
Nelilma C
NC
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.
Aguirre
Gabriela
G
Hernández
Paola
P
González
Mercedes
M
Cerecetto
Hugo
H
Aldana
Ignacio
I
Pérez-Silanes
Silvia
S
Monge
Antonio
A
Barreiro
Eliezer J
EJ
Lima
Lídia M
LM
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*
D015853:Cysteine Proteinase Inhibitors; D006835:Hydrazones; D015800:Protozoan Proteins; D011810:Quinoxalines; D014344:Trypanocidal Agents; D003546:Cysteine Endopeptidases; C074032:cruzain, Trypanosoma cruzi; D009547:Nifurtimox