In vitro and in vivo anti-Trypanosoma cruzi activity of a novel nitro-derivative.
Nitroarylidenemalononitriles and their cyanoacetamide derivatives with remarkable anti-epimastigote properties, were synthesized attempting to obtain new 3,5-diamino-4-(5'-nitroarylidene)-4H-thiadiazine 1,1-dioxide derivatives, which in previous reports had shown anti-Trypanosoma cruzi activity. Tests to evaluate the cytotoxicity of compounds were performed on J774 macrophages. 5-nitro-2-thienyl-malononitrile (5NO2TM), was the only product which maintained a high anti-epimastigote activity at concentrations in which it was no longer cytotoxic, thus it was assayed against intracellular amastigotes. Its anti-amastigote activity was similar to that of nifurtimox. Afterwards in vivo toxicity and anti-chagasic activity were determined. A reduction in parasitemia was observed.
Departamento de Parasitología, Facultad de Farmacia, Universidad Complutense, Madrid, España.
Susana
S
Muelas-Serrano
Ana
A
Le-Senne
Carlos
C
Fernandez-Portillo
Juan José
JJ
Nogal
Carmen
C
Ochoa
Alicia
A
Gomez-Barrio
D000818:Animals; D008264:Macrophages / Q000187:drug effects*; D008314:Malonates / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D009547:Nifurtimox / Q000494:pharmacology* / Q000633:toxicity; D009570:Nitriles / Q000494:pharmacology* / Q000633:toxicity; D021261:Parasitic Sensitivity Tests; D014344:Trypanocidal Agents / Q000494:pharmacology* / Q000633:toxicity; D014349:Trypanosoma cruzi / Q000187:drug effects*
C466759:5-nitro-2-thienylmalononitrile; D008314:Malonates; D009570:Nitriles; D014344:Trypanocidal Agents; D009547:Nifurtimox