Prospecting and Identifying Phyllanthus amarus Lignans with Antileishmanial and Antitrypanosomal Activity.

ABSTRACT

Ten lignans (1  - 10 ) were isolated from the hexane-ethyl acetate extract of Phyllanthus amarus leaves. 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 from P. amarus. Among the lignans tested against Trypanosoma cruzi intracellular amastigotes, 2 was the most active with an EC50 of 35.28 µM. Lignans 2, 5, 7 , and 9 showed inhibitory effects against Leishmania amazonensis promastigotes with EC50 of 56.34, 51.86, 23.57, and 43.27 µM, respectively. During in vitro infection assays, 5 reduced amastigotes by 91% at 103.68 µM concentration, whereas 7 and 9 reduced amastigotes by approximately 84% at 47.5 and 86.04 µM, respectively. Lignans 5, 7 , and 9 were more potent in intracellular amastigotes with EC50 of 2.76, 8.30, and 15.83 µM, respectively, than in promastigotes. CC50 for all samples was > 100 µg/mL, thus revealing low cytotoxicity against macrophages, and selectivity against the parasite. L. amazonensis promastigotes treated with compounds 2 and 9 showed decreased respiratory control of 38% and 25%, respectively, suggesting a change in mitochondrial membrane potential and lower ATP production.