title: 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 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.
authors.affiliation: Department of Tropical Medicine, Casilla de Correo 2511, Instituto de Investigaciones en Ciencias de la Salud Asunción, Universidad Nacional de Asuncion, Paraguay.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Ferreira
authors.forename: Hector
authors.initials: H
authors.lastname: Nakayama
authors.forename: Antonieta Rojas
authors.initials: AR
authors.lastname: de Arias
authors.forename: Alicia
authors.initials: A
authors.lastname: Schinini
authors.forename: Ninfa Vera
authors.initials: NV
authors.lastname: de Bilbao
authors.forename: Elva
authors.initials: E
authors.lastname: Serna
authors.forename: Delphine
authors.initials: D
authors.lastname: Lagoutte
authors.forename: Flor
authors.initials: F
authors.lastname: Soriano-Agatón
authors.forename: Erwan
authors.initials: E
authors.lastname: Poupon
authors.forename: Reynald
authors.initials: R
authors.lastname: Hocquemiller
authors.forename: Alain
authors.initials: A
authors.lastname: Fournet
mesh_terms: 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*
chemical_list: D000470:Alkaloids; D002243:Carbolines; D026121:Indole Alkaloids; D007211:Indoles; D009287:Naphthyridines; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; C453379:canthin-6-one; C009999:benzonidazole