Efficacy of the bisbenzylisoquinoline alkaloids in acute and chronic Trypanosoma cruzi murine model.
We have shown previously that daphnoline and cepharanthine are active against Trypanosoma cruzi and inhibited trypanothione reductase. The effects of oral treatments with daphnoline, cepharanthine and benznidazole were examined in Balb/c mice infected with T. cruzi acutely and chronically. In acute infections, parasitaemia was significantly reduced in the daphnoline-treated mice compared with controls and benznidazole-treated mice. The parasitological cure rate was increased in mice treated with daphnoline. Fifty days after infection, the negative serological response in both models was significantly different for the three tested drugs. Daphnoline showed the highest negative serological rate (48%). In chronically infected mice treated with daphnoline, we were unable to detect parasites in 70% of mice. The results obtained of oral treatment of daphnoline suggest that this bisbenzylisoquinoline may be useful in the treatment of acute and chronic Chagas' disease. This was not seen with cepharanthine, an excellent trypanothione reductase inhibitor.
Fournet
A
A
Institut de Recherche pour le Développement, ex-ORSTOM, UR Sante, Paris, France. alain.fournet@wanadoo.fr
Rojas de Arias
A
A
Ferreira
M E
ME
Nakayama
H
H
Torres de Ortiz
S
S
Schinini
A
A
Samudio
M
M
Vera de Bilbao
N
N
Lavault
M
M
Bonté
F
F
D000208:Acute Disease; D000284:Administration, Oral; D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D044182:Benzylisoquinolines; D014355:Chagas Disease / Q000188:drug therapy*; D002908:Chronic Disease; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015151:Immunoblotting; D007546:Isoquinolines / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009593:Nitroimidazoles / Q000008:administration & dosage / Q000494:pharmacology; D018512:Parasitemia / Q000188:drug therapy; D014344:Trypanocidal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D052117:Benzodioxoles
D000470:Alkaloids; D044182:Benzylisoquinolines; D007546:Isoquinolines; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; C117762:daphnoline; C006947:cepharanthine; D052117:Benzodioxoles; C009999:benzonidazole