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

Ten lignans (1:  - 10: ) were isolated from the hexane-ethyl acetate extract of 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 . Among the lignans tested against intracellular amastigotes, 2: was the most active with an EC of 35.28 µM. Lignans 2, 5, 7: , and 9: showed inhibitory effects against promastigotes with EC of 56.34, 51.86, 23.57, and 43.27 µM, respectively. During 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 EC of 2.76, 8.30, and 15.83 µM, respectively, than in promastigotes. CC for all samples was > 100 µg/mL, thus revealing low cytotoxicity against macrophages, and selectivity against the parasite. 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.