Prospecting and Identifying Phyllanthus amarus Lignans with Antileishmanial and Antitrypanosomal Activity

Gabrielly Galdino Conrado; Nathalia Grazzia; Adriana da Silva S. de Oliveira; Caio Haddad Franco; Carolina Borsoi Moraes; Fernanda Ramos Gadelha; Danilo Ciccone Miguel; Vera Lucia Garcia

doi:10.1055/a-1179-1003

Planta Medica, Inhaltsverzeichnis

Planta Med 2020; 86(11): 782-789
DOI: 10.1055/a-1179-1003

Biological and Pharmacological Activity

Original Papers

Georg Thieme Verlag KG Stuttgart · New York

Prospecting and Identifying Phyllanthus amarus Lignans with Antileishmanial and Antitrypanosomal Activity

Gabrielly Galdino Conrado

¹Divisão de Química Orgânica e Farmacêutica, Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas, Paulínia, SP, Brazil

²Programa de Pós-graduação em Biociências e Tecnologia de Produtos Bioativos, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, SP, Brazil

,

Nathalia Grazzia

³Departamento de Biologia Animal, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, SP, Brazil

,

Adriana da Silva S. de Oliveira

¹Divisão de Química Orgânica e Farmacêutica, Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas, Paulínia, SP, Brazil

²Programa de Pós-graduação em Biociências e Tecnologia de Produtos Bioativos, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, SP, Brazil

,

Caio Haddad Franco

⁴Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Campinas, SP, Brazil

⁵Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil

,

Carolina Borsoi Moraes

⁴Laboratório Nacional de Biociências, Centro Nacional de Pesquisa em Energia e Materiais, Campinas, SP, Brazil

⁵Departamento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil

,

Fernanda Ramos Gadelha

⁶Departamento de Bioquímica e Biologia Tecidual, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, SP, Brazil

,

Danilo Ciccone Miguel

³Departamento de Biologia Animal, Instituto de Biologia, Universidade Estadual de Campinas, Campinas, SP, Brazil

,

Vera Lucia Garcia

¹Divisão de Química Orgânica e Farmacêutica, Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas, Paulínia, SP, Brazil

› Institutsangaben

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.

Key words

Phyllanthus amarus - Euphorbiaceae - lignans - Leishmania amazonensis - Trypanosoma cruzi - amastigotes

Volltext

Referenzen

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