Antileishmanial activity of meroditerpenoids from the macroalgae Cystoseira baccata

Detalhes bibliográficos
Autor(a) principal: Sousa, Carolina Bruno de
Data de Publicação: 2017
Outros Autores: Gangadhar, Katkam N., Morais, Thiago R., Conserva, Geanne A. A., Vizetto-Duarte, C, Pereira, H., Laurenti, Marcia D., Campino, Lenea, Levy, Debora, Uemi, Miriam, Barreira, Luísa, Custódio, L., Passero, Luiz Felipe D., Lago, Joao Henrique G., Varela, João
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10400.1/13197
Resumo: The development of novel drugs for the treatment of leishmaniases continues to be crucial to overcome the severe impacts of these diseases on human and animal health. Several bioactivities have been described in extracts from macroalgae belonging to the Cystoseira genus. However, none of the studies has reported the chemical compounds responsible for the antileishmanial activity observed upon incubation of the parasite with the aforementioned extracts. Thus, this work aimed to isolate and characterize the molecules present in a hexane extract of Cystoseira baccata that was found to be bioactive against Leishmania infantum in a previous screening effort. A bioactivity-guided fractionation of the C. baccata extract was carried out and the inhibitory potential of the isolated compounds was evaluated via the MIT assay against promastigotes and murine macrophages as well as direct counting against intracellular amastigotes. Moreover, the promastigote ultrastructure, DNA fragmentation and changes in the mitochondrial potential were assessed to unravel their mechanism of action. In this process, two antileishmanial meroditerpenoids, (3R)- and (3S)-tetraprenyltoluquinol (1a/1b) and (3R)- and (3S)-tetraprenyltoluquinone (2a/2b), were isolated. Compounds 1 and 2 inhibited the growth of the L. infantum promastigotes (IC50 = 44.9 +/- 4.3 and 94.4 +/- 10.1 mu M, respectively), inducing cytoplasmic vacuolization and the presence of coiled multilamellar structures in mitochondria as well as an intense disruption of the mitochondrial membrane potential. Compound 1 decreased the intracellular infection index (IC50 = 25.0 +/- 4.1 mu M), while compound 2 eliminated 50% of the intracellular amastigotes at a concentration > 88.0 mu M. This work identified compound 2 as a novel metabolite and compound 1 as a biochemical isolated from Cystoseira algae displaying antileishmanial activity. Compound 1 can thus be an interesting scaffold for the development of novel chemotherapeutic molecules for canine and human visceral leishmaniases studies. This work reinforces the evidence of the marine environment as source of novel molecules. (C) 2017 Elsevier Inc. All rights reserved.
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spelling Antileishmanial activity of meroditerpenoids from the macroalgae Cystoseira baccataMarine brown-algaeVisceral leishmaniasisCytotoxic activityIn-vitroDeathPromastigotesAmazonensisApoptosisInfectionAutophagyThe development of novel drugs for the treatment of leishmaniases continues to be crucial to overcome the severe impacts of these diseases on human and animal health. Several bioactivities have been described in extracts from macroalgae belonging to the Cystoseira genus. However, none of the studies has reported the chemical compounds responsible for the antileishmanial activity observed upon incubation of the parasite with the aforementioned extracts. Thus, this work aimed to isolate and characterize the molecules present in a hexane extract of Cystoseira baccata that was found to be bioactive against Leishmania infantum in a previous screening effort. A bioactivity-guided fractionation of the C. baccata extract was carried out and the inhibitory potential of the isolated compounds was evaluated via the MIT assay against promastigotes and murine macrophages as well as direct counting against intracellular amastigotes. Moreover, the promastigote ultrastructure, DNA fragmentation and changes in the mitochondrial potential were assessed to unravel their mechanism of action. In this process, two antileishmanial meroditerpenoids, (3R)- and (3S)-tetraprenyltoluquinol (1a/1b) and (3R)- and (3S)-tetraprenyltoluquinone (2a/2b), were isolated. Compounds 1 and 2 inhibited the growth of the L. infantum promastigotes (IC50 = 44.9 +/- 4.3 and 94.4 +/- 10.1 mu M, respectively), inducing cytoplasmic vacuolization and the presence of coiled multilamellar structures in mitochondria as well as an intense disruption of the mitochondrial membrane potential. Compound 1 decreased the intracellular infection index (IC50 = 25.0 +/- 4.1 mu M), while compound 2 eliminated 50% of the intracellular amastigotes at a concentration > 88.0 mu M. This work identified compound 2 as a novel metabolite and compound 1 as a biochemical isolated from Cystoseira algae displaying antileishmanial activity. Compound 1 can thus be an interesting scaffold for the development of novel chemotherapeutic molecules for canine and human visceral leishmaniases studies. This work reinforces the evidence of the marine environment as source of novel molecules. (C) 2017 Elsevier Inc. All rights reserved.Portuguese FCT CCMAR/Multi/04326/2013FAPESP [2013/16297-2, 2015/11936-2]CNPq [470853/2012-3]FCT doctoral grants [ SFRH/BD/105541/2014 ]FCT Investigator Programme [IF/00049/2012]Academic PressSapientiaSousa, Carolina Bruno deGangadhar, Katkam N.Morais, Thiago R.Conserva, Geanne A. A.Vizetto-Duarte, CPereira, H.Laurenti, Marcia D.Campino, LeneaLevy, DeboraUemi, MiriamBarreira, LuísaCustódio, L.Passero, Luiz Felipe D.Lago, Joao Henrique G.Varela, João2019-11-20T15:07:45Z2017-032017-03-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.1/13197eng0014-489410.1016/j.exppara.2017.01.002info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-24T10:25:16Zoai:sapientia.ualg.pt:10400.1/13197Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:04:23.267573Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Antileishmanial activity of meroditerpenoids from the macroalgae Cystoseira baccata
title Antileishmanial activity of meroditerpenoids from the macroalgae Cystoseira baccata
spellingShingle Antileishmanial activity of meroditerpenoids from the macroalgae Cystoseira baccata
Sousa, Carolina Bruno de
Marine brown-algae
Visceral leishmaniasis
Cytotoxic activity
In-vitro
Death
Promastigotes
Amazonensis
Apoptosis
Infection
Autophagy
title_short Antileishmanial activity of meroditerpenoids from the macroalgae Cystoseira baccata
title_full Antileishmanial activity of meroditerpenoids from the macroalgae Cystoseira baccata
title_fullStr Antileishmanial activity of meroditerpenoids from the macroalgae Cystoseira baccata
title_full_unstemmed Antileishmanial activity of meroditerpenoids from the macroalgae Cystoseira baccata
title_sort Antileishmanial activity of meroditerpenoids from the macroalgae Cystoseira baccata
author Sousa, Carolina Bruno de
author_facet Sousa, Carolina Bruno de
Gangadhar, Katkam N.
Morais, Thiago R.
Conserva, Geanne A. A.
Vizetto-Duarte, C
Pereira, H.
Laurenti, Marcia D.
Campino, Lenea
Levy, Debora
Uemi, Miriam
Barreira, Luísa
Custódio, L.
Passero, Luiz Felipe D.
Lago, Joao Henrique G.
Varela, João
author_role author
author2 Gangadhar, Katkam N.
Morais, Thiago R.
Conserva, Geanne A. A.
Vizetto-Duarte, C
Pereira, H.
Laurenti, Marcia D.
Campino, Lenea
Levy, Debora
Uemi, Miriam
Barreira, Luísa
Custódio, L.
Passero, Luiz Felipe D.
Lago, Joao Henrique G.
Varela, João
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Sapientia
dc.contributor.author.fl_str_mv Sousa, Carolina Bruno de
Gangadhar, Katkam N.
Morais, Thiago R.
Conserva, Geanne A. A.
Vizetto-Duarte, C
Pereira, H.
Laurenti, Marcia D.
Campino, Lenea
Levy, Debora
Uemi, Miriam
Barreira, Luísa
Custódio, L.
Passero, Luiz Felipe D.
Lago, Joao Henrique G.
Varela, João
dc.subject.por.fl_str_mv Marine brown-algae
Visceral leishmaniasis
Cytotoxic activity
In-vitro
Death
Promastigotes
Amazonensis
Apoptosis
Infection
Autophagy
topic Marine brown-algae
Visceral leishmaniasis
Cytotoxic activity
In-vitro
Death
Promastigotes
Amazonensis
Apoptosis
Infection
Autophagy
description The development of novel drugs for the treatment of leishmaniases continues to be crucial to overcome the severe impacts of these diseases on human and animal health. Several bioactivities have been described in extracts from macroalgae belonging to the Cystoseira genus. However, none of the studies has reported the chemical compounds responsible for the antileishmanial activity observed upon incubation of the parasite with the aforementioned extracts. Thus, this work aimed to isolate and characterize the molecules present in a hexane extract of Cystoseira baccata that was found to be bioactive against Leishmania infantum in a previous screening effort. A bioactivity-guided fractionation of the C. baccata extract was carried out and the inhibitory potential of the isolated compounds was evaluated via the MIT assay against promastigotes and murine macrophages as well as direct counting against intracellular amastigotes. Moreover, the promastigote ultrastructure, DNA fragmentation and changes in the mitochondrial potential were assessed to unravel their mechanism of action. In this process, two antileishmanial meroditerpenoids, (3R)- and (3S)-tetraprenyltoluquinol (1a/1b) and (3R)- and (3S)-tetraprenyltoluquinone (2a/2b), were isolated. Compounds 1 and 2 inhibited the growth of the L. infantum promastigotes (IC50 = 44.9 +/- 4.3 and 94.4 +/- 10.1 mu M, respectively), inducing cytoplasmic vacuolization and the presence of coiled multilamellar structures in mitochondria as well as an intense disruption of the mitochondrial membrane potential. Compound 1 decreased the intracellular infection index (IC50 = 25.0 +/- 4.1 mu M), while compound 2 eliminated 50% of the intracellular amastigotes at a concentration > 88.0 mu M. This work identified compound 2 as a novel metabolite and compound 1 as a biochemical isolated from Cystoseira algae displaying antileishmanial activity. Compound 1 can thus be an interesting scaffold for the development of novel chemotherapeutic molecules for canine and human visceral leishmaniases studies. This work reinforces the evidence of the marine environment as source of novel molecules. (C) 2017 Elsevier Inc. All rights reserved.
publishDate 2017
dc.date.none.fl_str_mv 2017-03
2017-03-01T00:00:00Z
2019-11-20T15:07:45Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.identifier.uri.fl_str_mv http://hdl.handle.net/10400.1/13197
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dc.language.iso.fl_str_mv eng
language eng
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10.1016/j.exppara.2017.01.002
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dc.publisher.none.fl_str_mv Academic Press
publisher.none.fl_str_mv Academic Press
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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