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Phloroglucinol derivatives from Hypericum species trigger mitochondrial dysfunction in Leishmania amazonensis

Published online by Cambridge University Press:  27 February 2018

Ana Paula Aquistapase Dagnino ,
Camila Saporiti Mesquita ,
Gilson Pires Dorneles ,
Vivian de Oliveira Nunes Teixeira ,
Francisco Maikon Corrêa de Barros ,
Gari Vidal Ccana-Ccapatinta ,
Simone Gonçalves Fonseca ,
Marta Chagas Monteiro ,
Luiz Carlos Rodrigues Júnior  and
Alessandra Peres
...Show all authors
Ana Paula Aquistapase Dagnino
Affiliation:
Laboratório de Imunologia, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil
Camila Saporiti Mesquita
Affiliation:
Laboratório de Imunologia, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil
Gilson Pires Dorneles
Affiliation:
Laboratório de Imunologia, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil
Vivian de Oliveira Nunes Teixeira
Affiliation:
Laboratório de Imunologia, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil
Francisco Maikon Corrêa de Barros
Affiliation:
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Av. Ipiranga 2752, 90610-000 Porto Alegre, RS, Brazil
Gari Vidal Ccana-Ccapatinta
Affiliation:
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Av. Ipiranga 2752, 90610-000 Porto Alegre, RS, Brazil
Simone Gonçalves Fonseca
Affiliation:
Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, 74605-050 Goiania, GO, Brazil
Marta Chagas Monteiro
Affiliation:
Programa de Pós-graduação em Ciências Farmacêuticas, Instituto de Ciências da Saúde, Universidade Federal do Pará/UFPA, 66075-110 Belém, PA, Brazil
Luiz Carlos Rodrigues Júnior
Affiliation:
Laboratório de Imunologia, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil
Alessandra Peres
Affiliation:
Laboratório de Imunologia, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil Programa de Pós-Graduação em Ciências da Reabilitação, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil Centro Universitário Metodista IPA, Rua Coronel Joaquim Pedro Salgado, 80, 90420-060, Porto Alegre, RS, Brazil
Gilsane Lino von Poser
Affiliation:
Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Av. Ipiranga 2752, 90610-000 Porto Alegre, RS, Brazil
Pedro Roosevelt Torres Romão*
Affiliation:
Laboratório de Imunologia, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil Programa de Pós-Graduação em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil
*
Author for correspondence: Pedro Roosevelt Torres Romão, E-mail: [email protected]
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Abstract

Bioactive molecules isolated from plants are promising sources for the development of new therapies against leishmaniasis. We investigated the leishmanicidal activity of cariphenone A (1), isouliginosin B (2) and uliginosin B (3) isolated from Hypericum species. Promastigotes and amastigotes of Leishmania amazonensis were incubated with compounds 1–3 at concentrations 1–100 µm for 48 h. The anti-promastigote effect of compounds was also tested in combinations. The cytotoxicity against macrophages and human erythrocytes were determined using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) method and hemolysis assay, respectively. The compounds 1–3 showed high leishmanicidal activity against promastigotes, IC50 values of 10.5, 17.5 and 11.3 µm, respectively. Synergistic interactions were found to the associations of compounds 1 and 2 [Σ fractional inhibitory concentration (FIC) = 0.41], and 2 and 3 (ΣFIC = 0.28) on promastigotes. All Hypericum compounds induced mitochondrial hyperpolarization and reactive oxygen species production in promastigotes. The compounds showed low cytotoxicity toward mammalian cells, high selectivity index and killed intracellular amastigotes probably mediated by oxidative stress. These results indicate that these compounds are promising candidates for the development of drugs against leishmaniasis.

Keywords

Cariphenone AIsouliginosin BLeishmanicidal activityReactive oxygen speciesUliginosin B
Type
Research Article
Information
Parasitology , Volume 145 , Issue 9 , August 2018 , pp. 1199 - 1209
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Copyright
Copyright © Cambridge University Press 2018 

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