Effects of canthin-6-one alkaloids from Zanthoxylum chiloperone on Trypanosoma cruzi-infected mice.
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 5mg/kg/day for 2 weeks, whereas the alkaloidal extract was given at 50mg/kg/day for 2 weeks. The antiparasitic activity was compared with that of benznidazole given at 50mg/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.
Ferreira
Maria Elena
ME
Department of Tropical Medicine, Casilla de Correo 2511, Instituto de Investigaciones en Ciencias de la Salud Asunción, Universidad Nacional de Asuncion, Paraguay.
Nakayama
Hector
H
de Arias
Antonieta Rojas
AR
Schinini
Alicia
A
de Bilbao
Ninfa Vera
NV
Serna
Elva
E
Lagoutte
Delphine
D
Soriano-Agatón
Flor
F
Poupon
Erwan
E
Hocquemiller
Reynald
R
Fournet
Alain
A
D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002243:Carbolines; D014355:Chagas Disease / Q000188:drug therapy* / Q000401:mortality; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D026121:Indole Alkaloids; D007211:Indoles / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009287:Naphthyridines / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D009593:Nitroimidazoles / Q000494:pharmacology; D015996:Survival Rate; D014344:Trypanocidal Agents / Q000737:chemistry / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000472:pathogenicity*; D032106:Zanthoxylum / Q000737:chemistry*
D000470:Alkaloids; D002243:Carbolines; D026121:Indole Alkaloids; D007211:Indoles; D009287:Naphthyridines; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; C453379:canthin-6-one; C009999:benzonidazole