Efficacy of the bisbenzylisoquinoline alkaloids in acute and chronic Trypanosoma cruzi murine model

We have shown previously that daphnoline and cepharanthine are active again st Trypanosoma cruzi and inhibited trypanothione reductase. The effects of oral treatments with daphnoline, cepharanthine and benznidazole were examin ed in Balb/c mice infected with T. cruzi acutely and chronically. In acute infections, parasitaemia was significantly reduced in the daphnoline-treate d mice compared with controls and benznidazole-treated mice. The parasitolo gical cure rate was increased in mice treated with daphnoline. Fifty days a fter infection, the negative serological response in both models was signif icantly 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 bisbenzylisoqui noline may be useful in the treatment of acute and chronic Chagas' disease. This was not seen with cepharanthine, an excellent trypanothione reductase inhibitor. (C) 2000 Elsevier Science B.V. and International Society of Che motherapy. All rights reserved.