In Vitro Cytotoxic and Leishmanicidal Activity of Isolated and Semisynthetic ent-Pimaranes from Aldama arenaria.

Two pimaranes ent-pimara-8(14),15-dien-19-oic acid (1: ) and ent-8(14),15-pimaradien-3ß-ol (2: ), isolated from Aldama arenaria, and six semi-synthetic derivatives methyl ester of the ent-pimara-8(14),15-dien-19-oic acid (3: ), ent-pimara-8(14),15-dien-19-ol (4: ), acetate of ent-pimara-8(14),15-dien-19-ol (5: ), ent-pimara-8(14),15-dien-19-ol succinic acid (6: ), acetate of ent-8(14),15-pimaradien-3ß-ol (7: ), ent-8(14),15-pimaradien-3ß-ol succinic acid (8: ) were evaluated in vitro for their cytotoxic activities to childhood leukemia cell lines and leishmanicidal activity against the parasite Leishmania amazonensis. Among these compounds, 1: to 6: presented moderate cytotoxic activity, with compound 4: being the most active (GI50 of 2.6 µM for the HL60 line) and the derivatives 7: and 8: being inactive. Against the parasite Leishmania amazonensis, the most promising derivative was the acetate of ent-pimara-8(14),15-dien-19-ol (5: ), with EC50 of 20.1 µM, selectivity index of 14.5, and significant reduction in the parasite load. Pimarane analogues 1: , ent-pimara-8(14),15-dien-19-oic acid, and 2: , ent-8(14),15-pimaradien-3ß-ol, presented different activities, corroborating the application of such molecules as prototypes for the design of other derivatives that have greater cytotoxic or leishmanicidal potential.

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

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.

Anti-inflammatory, anti-hyperalgesic, antiplatelet and antiulcer activities of Byrsonima japurensis A. Juss. (Malpighiaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Decoctions or infusions of the stem bark of Byrsonima japurensis A. Juss. (Malpighiaceae) are widely used as an anti-inflammatory drug in folk medicine of Amazonas State (Brazil). AIM OF THE STUDY: To evaluate the pharmacological potential of an aqueous extract of the stem bark of Byrsonima japurensis (BJEA) to scientifically verify of its traditional use. MATERIALS AND METHODS: Anti-inflammatory, antihyperalgesic and antiulcer activities were evaluated in Wistar rats, a Hippocratic screening was performed in Swiss mice to evaluate the toxic effects, and antiplatelet evaluation was performed in human platelet rich plasma assay. Additionally, antioxidant activity was evaluated by superoxide radical scavenging method and ß-carotene bleaching test. RESULTS: Anti-inflammatory, antihyperalgesic and gastroprotective activities were observed in rats treated orally with different doses of BJEA. While signals of toxicity were observed in the mice treated with a very high dose of extract (5000mg/kg), no death occurred. BJEA also showed expressive antiplatelet and antioxidant activities in vitro. CONCLUSION: According to our results, it was concluded that stem bark of Byrsonima japurensis has significant and safe anti-inflammatory activity, which is closely related with their potent antioxidant activity, supporting the folk medicinal use of this species.