Prospecting and IdentifyingPhyllanthus amarusLignans with Antileishmanial and Antitrypanosomal Activity

Author(s)

Conrado, Gabrielly Galdino ^{[1, 2]} ; Grazzia, Nathalia ^[3] ; de Oliveira, Adriana da Silva S. ^{[1, 2]} ; Franco, Caio Haddad ^{[4, 5]} ; Moraes, Carolina Borsoi ^{[4, 5]} ; Gadelha, Fernanda Ramos ^[6] ; Miguel, Danilo Ciccone ^[3] ; Garcia, Vera Lucia ^[1]

Affiliation

^[1] Ctr Pluridisciplinar Pesquisas Quim Biol & Agr, Div Quim Organ & Farmaceut, Paulinia, SP - Brazil

^[2] Univ Estadual Campinas, Inst Biol, Programa Posgrad Biociencias & Tecnol Prod Bioati, Campinas, SP - Brazil

^[3] Univ Estadual Campinas, Inst Biol, Dept Biol Anim, Campinas, SP - Brazil

^[4] Ctr Nacl Pesquisa Energia & Mat, Lab Nacl Biociencias, Campinas, SP - Brazil

^[5] Univ Sao Paulo, Inst Ciencias Biomed, Dept Microbiol, Sao Paulo, SP - Brazil

^[6] Univ Estadual Campinas, Inst Biol, Dept Bioquim & Biol Tecidual, Campinas, SP - Brazil

• Document type: Journal article
• Source: Planta Medica; v. 86, n. 11, p. 782-789, JUL 2020.
• Web of Science Citations: 1

Abstract

Ten lignans (1 - 10) were isolated from the hexane-ethyl acetate extract ofPhyllanthus amarusleaves. 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 fromP. amarus. Among the lignans tested againstTrypanosoma cruziintracellular amastigotes,2was the most active with an EC(50)of 35.28 mu M. Lignans2, 5, 7, and9showed inhibitory effects againstLeishmania amazonensispromastigotes with EC(50)of 56.34, 51.86, 23.57, and 43.27 mu M, respectively. Duringin vitroinfection assays,5reduced amastigotes by 91% at 103.68 mu M concentration, whereas7and9reduced amastigotes by approximately 84% at 47.5 and 86.04 mu M, respectively. Lignans5, 7, and9were more potent in intracellular amastigotes with EC(50)of 2.76, 8.30, and 15.83 mu M, respectively, than in promastigotes. CC(50)for all samples was > 100 mu g/mL, thus revealing low cytotoxicity against macrophages, and selectivity against the parasite.L. amazonensispromastigotes treated with compounds2and9showed decreased respiratory control of 38% and 25%, respectively, suggesting a change in mitochondrial membrane potential and lower ATP production. (AU)

• FAPESP's process: 09/16858-9 - Activity study of the isolated compounds from the ethanolic extract of the Phyllanthus amarus L. against Schistosoma mansoni BH
• Grantee: Vera Lúcia Garcia
• Support Opportunities: Regular Research Grants