In vivo studies of 5-arylethenylbenzofuroxans in acute murine models of Chagas' disease.
5-arylethenylbenzofuroxan derivatives with high in vitro anti-Trypanosoma cruzi activity were studied in vivo using acute murine models of Chagas' disease. The selected compounds, as pure isomeric forms, 1, 2, 3 and 4, or as equimolecular mixture of geometric isomers, 1:2, 3:4, 5:6 were studied against different T. cruzi strains. Consequently, Tulahuen 2 strain, Colombiana strain (resistant to Nifurtimox and Benznidazole), and two different wild strains, one isolated from the wild reservoir Didelphis marsupialis and another one from Uruguayan patients, were selected. No relevant signs of in vivo toxicity were observed with the benzofuroxans orally administered. Compound 1 and the mixture of isomers 1:2 were the best for treating infection against the four studied strains.
Boiani
Lucía
L
Departamento de Química Orgánica, Facultad de Química-Facultad de Ciencias, Universidad de la República, Iguá 4225, 11400 Montevideo, Uruguay.
Davies
Carolina
C
Arredondo
Carolina
C
Porcal
Williams
W
Merlino
Alicia
A
Gerpe
Alejandra
A
Boiani
Mariana
M
Pacheco
José Pedro
JP
Basombrío
Miguel Angel
MA
Cerecetto
Hugo
H
González
Mercedes
M
D000208:Acute Disease / Q000628:therapy; D000818:Animals; D000913:Antibodies, Protozoan / Q000378:metabolism; D001583:Benzoxazoles / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D014355:Chagas Disease / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000628:therapy; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D018512:Parasitemia / Q000188:drug therapy; D016896:Treatment Outcome; D014349:Trypanosoma cruzi / Q000187:drug effects; D010069:Oxadiazoles
D000913:Antibodies, Protozoan; D001583:Benzoxazoles; C014354:benzofuroxan; D010069:Oxadiazoles