Antileishmanial activity of meroditerpenoids from the macroalgae Cystoseira baccata
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , , , , , , , |
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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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 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.1/13197 |
url |
http://hdl.handle.net/10400.1/13197 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0014-4894 10.1016/j.exppara.2017.01.002 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Academic Press |
publisher.none.fl_str_mv |
Academic Press |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799133280941899776 |