Effects of canthin-6-one alkaloids from Zanthoxylum chiloperone on Trypanosoma cruzi-infected mice

Abstract

Canthin-6-one ( 1), isolated from Zanthoxylum chiloperone ( Rutaceae), possesses a broad sprectum of antifungal and leishmanicidal activities. In this study, we have examined the antiparasitic effects of canthin-6-one ( 1), 5-methoxycanthin-6-one ( 2), canthin-6-one N-oxide ( 3), as well as that of the total alkaloids of Zanthoxylum chiloperone stem bark, in Balb/c mice infected either acutely or chronically with Trypanosoma cruzi. The compounds were administered orally or subcutaneously at 5 mg/kg/day for 2 weeks, whereas the alkaloidal extract was given at 50 mg/kg/day for 2 weeks. The antiparasitic activity was compared with that of benznidazole given at 50 mg/kg/day for 2 weeks. In the case of acute infection, parasiteamia was significantly reduced following oral treatment with canthin-6-one ( 1). Moreover, the total alkaloids of Zanthoxylum chiloperone stem bark led to high levels of parasitological clearance. Seventy days post-infection, the serological response in the acute model was significantly different between oral canthin-6-one ( 1) and benznidazole-treated mice. Chronic model of the disease showed that both canthin-6-one ( 1) and the alkaloidal extract at the above dosage induced 80–100% animal survival compared to untreated controls. These results indicate that canthin-6-one ( 1) exhibits trypanocidal activity in vivo in the mouse model of acute or chronic infection. This is the first demonstration of anti- Trypanosoma cruzi activity for a member of this chemical group (canthinones). Considering the very low toxicity of canthin-6-one ( 1), our results suggest that long-term oral treatment with this natural product could prove advantageous compared to the current chemotherapy of Chagas disease.