Northalrugosidine Is a Bisbenzyltetrahydroisoquinoline Alkaloid from Thalictrum alpinum with in Vivo Antileishmanial Activity

摘要

Screening of a plant-derived natural product library led to the observation of in vitro antileishmanial activity by three bisbenzyltetrahydroisoquinoline alkaloids (1-3) that were purified previously from Thalictrum alpinum. A spectroscopic study of the active compounds was conducted to confirm their identities. Of the compounds tested, northalrugosidine (1) showed the most potent in vitro activity against Leishmania donovani promastigotes (0.28 mu M) and the highest selectivity (29.3-fold) versus its general cytotoxicity against HT-29 human colon adenocarcinoma cells. Northalrugosidine was tested in vivo using a murine model of visceral leishmaniasis, resulting in the observation of a dose-dependent reduction of the parasitic burden in the liver and spleen without overt toxicity effects at 2.8, 5.6, and 11.1 mg/kg per animal when administered intravenously. This represents the first report of a bisbenzyltetrahydroisoquinoline alkaloid with in vivo efficacy against visceral leishmaniasis.