Prospecting And Identifyingphyllanthus Amaruslignans With Antileishmanial And Antitrypanosomal Activity

Ten lignans (1 - 10) were isolated from the hexane-ethyl acetate extract ofPhyllanthus amarusleaves. Three of them, cubebin dimethyl ether (3), urinatetralin (4), and lintetralin (7) are described for the first time in this species, while phyllanthin (1), niranthin (2), 5-demethoxyniranthin (5), isolintetralin (6), hypophyllanthin (8), nirtetralin (9), and phyltetralin (10) have been already reported fromP. amarus. Among the lignans tested againstTrypanosoma cruziintracellular amastigotes,2was the most active with an EC(50)of 35.28 mu M. Lignans2, 5, 7, and9showed inhibitory effects againstLeishmania amazonensispromastigotes with EC(50)of 56.34, 51.86, 23.57, and 43.27 mu M, respectively. Duringin vitroinfection assays,5reduced amastigotes by 91% at 103.68 mu M concentration, whereas7and9reduced amastigotes by approximately 84% at 47.5 and 86.04 mu M, respectively. Lignans5, 7, and9were more potent in intracellular amastigotes with EC(50)of 2.76, 8.30, and 15.83 mu M, respectively, than in promastigotes. CC(50)for all samples was > 100 mu g/mL, thus revealing low cytotoxicity against macrophages, and selectivity against the parasite.L. amazonensispromastigotes treated with compounds2and9showed decreased respiratory control of 38% and 25%, respectively, suggesting a change in mitochondrial membrane potential and lower ATP production.