Prospecting and Identifying Phyllanthus amarus Lignans with Antileishmanial and Antitrypanosomal Activity

  • Planta Med. 2020 Jul;86(11):782-789. doi: 10.1055/a-1179-1003.
Gabrielly Galdino Conrado  1  2 ,  Nathalia Grazzia  3 ,  Adriana da Silva S de Oliveira  1  2 ,  Caio Haddad Franco  4  5 ,  Carolina Borsoi Moraes  4  5 ,  Fernanda Ramos Gadelha  6 ,  Danilo Ciccone Miguel  3 ,  Vera Lucia Garcia  1
Affiliations
  • 1. Divisão de Química Orgânica e Farmacêutica, Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas, Paulínia, SP, Brazil.
  • 2. Programa de Pós-graduação em Biociências e Tecnologia de Produtos Bioativos, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, SP, Brazil.
  • 3. Departamento de Biologia Animal, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, SP, Brazil.
  • 4. Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Campinas, SP, Brazil.
  • 5. Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil.
  • 6. Departamento de Bioquímica e Biologia Tecidual, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, SP, Brazil.
PMID: 32512613 DOI: 10.1055/a-1179-1003
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.

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