Phaeurus antarcticus and its endophytic fungi: chemical diversity of a hidden pharmacy underneath the Antarctic Ocean
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Tipo de documento: | Tese |
Idioma: | eng |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da USP |
Texto Completo: | https://www.teses.usp.br/teses/disponiveis/60/60138/tde-20072023-113231/ |
Resumo: | Chapter I: The chemical profile and antibacterial, antiparasitic, and insecticidal activities of the seaweed P. antarcticus were investigated. The hexane extract (HX) and its fractions exhibited selective antibacterial activity against Staphylococcus aureus. Fractions HX-FC and HX-FD showed the highest antiparasitic activity against Leishmania amazonensis and Neospora caninum. The HX extract and the HX-FC fraction presented insecticidal potential against Aedes aegypti larvae. Through GC-MS analysis and the combination of multivariate statistical analyses (OPLS-DA) and the construction of molecular networks (GNPS), it was possible to annotate terpenes, steroids, fatty acids, and alcohols in the bioactive fractions. Chapter II: Using metabolomics techniques (UPLC-HRMS/1H NMR) and multivariate statistical analysis (PCA, OPLS-DA), the spatial variability of secondary metabolites of the seaweed P. antarcticus and the antibiofilm activity of extracts and fractions were evaluated against S. aureus resistant to methicillin-oxacillin (MRSA). The results revealed that the changes in the chemical profile were not site-specific and could be related to different life cycle stages of the collected algae. Porphyrins, terpenes, and carotenoids were annotated as discriminating compounds. Linoleic acid (1) and fucosterol (2) were isolated from the bioactive fractions and showed antibiofilm activity against MRSA. Chapter III: The extract and fractions of the fungus Penicillium purpurogenum were evaluated for antibacterial, antiparasitic, immunomodulatory, and photoprotective activities. The bioguided fractionation led to the isolation of six polyketides: 5,6,8-trihydroxy-4-(1\'-hydroxyethyl) isocoumarin (3), aspergillumarin A (4), aspergillumarin B (5), Berkeleyacetal C (6), sescandelin (7), and vermistatin (8). Compounds 3, 4, 7, and 8 presented photostability and photoprotective activities against UVB-UVA. Compounds 3, 6, 7, and 8 presented immunomodulatory activity by down-regulating the production of reactive oxygen species in PMA-stimulated human neutrophils without cytotoxic effects. Compound 6 presented leishmanicidal activity against amastigotes of L. amazonensis. Chapter IV: The chemical profile (UPLC-HRMS/1H NMR) and antibiofilm activity against MRSA of 21 fungal strains were investigated. Among them, the fractionation of the extract of the fungus Epicoccum nigrum led to the isolation of epicorazines A-B (9-10) and C (12) as well as a new terpenoid (11). Compound 9-12 exhibited antibiofilm activity against MRSA. Among these, compound 11 showed the highest inhibition of pre-biofilm formation and rupture of the formed biofilm. Given the global context, this work sought to obtain new biotechnological products, considering the United Nations Sustainable Development Goals. The results obtained provide new information about the chemotaxonomy and biotechnological potential of Antarctic marine organisms as producers of biomolecules of pharmaceutical interest, emphasizing the importance of bioprospecting for the conservation of understudied organisms. |
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Phaeurus antarcticus and its endophytic fungi: chemical diversity of a hidden pharmacy underneath the Antarctic OceanPhaeurus antarcticus e seus fungos endofíticos: diversidade química de uma farmácia oculta sob o oceano AntárticoAntarctic fungiAntarctic seaweedAntimicrobialsAntimicrobianosAtividade imunomoduladoraDoenças negligenciadasFotoproteçãoFungos antárticosImmunomodulatory activityMacroalgas antárticasMarine natural productsMetabolômicaMetabolomicsNeglected diseasesPhotoprotectionProdutos naturais marinhosChapter I: The chemical profile and antibacterial, antiparasitic, and insecticidal activities of the seaweed P. antarcticus were investigated. The hexane extract (HX) and its fractions exhibited selective antibacterial activity against Staphylococcus aureus. Fractions HX-FC and HX-FD showed the highest antiparasitic activity against Leishmania amazonensis and Neospora caninum. The HX extract and the HX-FC fraction presented insecticidal potential against Aedes aegypti larvae. Through GC-MS analysis and the combination of multivariate statistical analyses (OPLS-DA) and the construction of molecular networks (GNPS), it was possible to annotate terpenes, steroids, fatty acids, and alcohols in the bioactive fractions. Chapter II: Using metabolomics techniques (UPLC-HRMS/1H NMR) and multivariate statistical analysis (PCA, OPLS-DA), the spatial variability of secondary metabolites of the seaweed P. antarcticus and the antibiofilm activity of extracts and fractions were evaluated against S. aureus resistant to methicillin-oxacillin (MRSA). The results revealed that the changes in the chemical profile were not site-specific and could be related to different life cycle stages of the collected algae. Porphyrins, terpenes, and carotenoids were annotated as discriminating compounds. Linoleic acid (1) and fucosterol (2) were isolated from the bioactive fractions and showed antibiofilm activity against MRSA. Chapter III: The extract and fractions of the fungus Penicillium purpurogenum were evaluated for antibacterial, antiparasitic, immunomodulatory, and photoprotective activities. The bioguided fractionation led to the isolation of six polyketides: 5,6,8-trihydroxy-4-(1\'-hydroxyethyl) isocoumarin (3), aspergillumarin A (4), aspergillumarin B (5), Berkeleyacetal C (6), sescandelin (7), and vermistatin (8). Compounds 3, 4, 7, and 8 presented photostability and photoprotective activities against UVB-UVA. Compounds 3, 6, 7, and 8 presented immunomodulatory activity by down-regulating the production of reactive oxygen species in PMA-stimulated human neutrophils without cytotoxic effects. Compound 6 presented leishmanicidal activity against amastigotes of L. amazonensis. Chapter IV: The chemical profile (UPLC-HRMS/1H NMR) and antibiofilm activity against MRSA of 21 fungal strains were investigated. Among them, the fractionation of the extract of the fungus Epicoccum nigrum led to the isolation of epicorazines A-B (9-10) and C (12) as well as a new terpenoid (11). Compound 9-12 exhibited antibiofilm activity against MRSA. Among these, compound 11 showed the highest inhibition of pre-biofilm formation and rupture of the formed biofilm. Given the global context, this work sought to obtain new biotechnological products, considering the United Nations Sustainable Development Goals. The results obtained provide new information about the chemotaxonomy and biotechnological potential of Antarctic marine organisms as producers of biomolecules of pharmaceutical interest, emphasizing the importance of bioprospecting for the conservation of understudied organisms.Capítulo I: O perfil químico e as atividades antibacteriana, antiparasitária e inseticida da alga P. antarcticus foram investigados. O extrato hexânico (HX) e suas frações exibiram atividade bacteriostática e bactericida seletiva contra Staphylococcus. aureus. As frações HX-FC e HX-FD apresentaram atividade antiparasitária frente a Leishmania amazonensis e Neospora caninum. O extrato HX e a fração HX-FC apresentaram potencial inseticida frente a larvas de Aedes aegypti. Através de análises em CG-EM, e combinação de análises estatísticas multivariadas (OPLS-DA) com a construção de redes moleculares (GNPS) foi possível anotar terpenos, esteroides ácidos graxos e álcoois nas frações bioativas. Capítulo II: Utilizando técnicas metabolômicas (CLUE-EM/RMN 1H) combinadas a análises estatísticas multivariadas (PCA, OPLS-DA) a variabilidade espacial de metabólitos secundários da alga P. antarcticus e a atividade antibiofilme dos extratos e frações foram avaliados frente a S. aureus resistente à meticilina e oxacilina (MRSA). Os resultados revelaram que as mudanças no perfil químico não foram sítio específicas e podem estar relacionadas a diferentes estágios do ciclo de vida das algas coletadas. Porfirinas, terpenos e carotenoides foram anotados como sustâncias discriminantes. O ácido linoleico (1) e o fucosterol (2) foram isolados das frações bioativas e apresentaram atividade antibiofilme frente a MRSA. Capítulo III: O extrato e frações do fungo Penicillium purpurogenum foram submetidos a avaliação das atividades antibacteriana, antiparasitária, imunomoduladora e fotoprotetora. O fracionamento bioguiado levou ao isolamento de seis policetídeos: 5,6,8-triidroxi-4-(1´-hidroxietil) isocumarina (3), aspergilumarina A (4), aspergilumarina B (5) berkeleyacetal C (6), sescandelina (7) e vermistatina (8). O potencial fotoprotetor, imunomodulador e leishmanicida das substâncias foi avaliado. As substâncias 3, 4, 7 e 8 apresentaram fotoestabilidade e atividade fotoprotetora frente a radiação UVB-UVA. As substâncias 3, 6, 7 e 8 apresentaram potencial imunomodulador, reduzindo a produção de espécies reativas de oxigênio em neutrófilos humanos estimulados pelo PMA sem efeitos citotóxicos. A substância 6 apresentou atividade leishmanicida frente a amastigotas de L. amazonensis. Capítulo IV: O perfil químico (CLUE-EM/ RMN 1H) e a atividade antibiofilme frente a MRSA de 21 linhagens fúngicas foram investigados. O fracionamento do extrato do fungo Epicoccum nigrum, levou ao isolamento das epicozarinas A - B (9-10) e C (12) e de um terpeno (11) inédito. As substâncias 9 - 12 exibiram atividade antibiofilme contra MRSA. Dentre estas, a substância 11 apresentou maior inibição da formação de pré-biofilme e ruptura do biofilme formado. Diante do contexto global, este trabalho buscou a obtenção de novos produtos biotecnológicos, considerando os Objetivos do Desenvolvimento Sustentável das Nações Unidas. Os resultados obtidos fornecem novas informações quimio-taxonômicas e potencial biotecnológico dos organismos marinhos da Antártica como produtores de biomoléculas de interesse farmacêutico, enfatizando a importância da bioprospecção para a conservação de organismos ainda pouco conhecidos.Biblioteca Digitais de Teses e Dissertações da USPDebonsi, Hosana MariaEdrada-ebel, Ru AngelieSantos, Gustavo Souza dos2022-11-29info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfhttps://www.teses.usp.br/teses/disponiveis/60/60138/tde-20072023-113231/reponame:Biblioteca Digital de Teses e Dissertações da USPinstname:Universidade de São Paulo (USP)instacron:USPLiberar o conteúdo para acesso público.info:eu-repo/semantics/openAccesseng2024-11-29T13:00:02Zoai:teses.usp.br:tde-20072023-113231Biblioteca Digital de Teses e Dissertaçõeshttp://www.teses.usp.br/PUBhttp://www.teses.usp.br/cgi-bin/mtd2br.plvirginia@if.usp.br|| atendimento@aguia.usp.br||virginia@if.usp.bropendoar:27212024-11-29T13:00:02Biblioteca Digital de Teses e Dissertações da USP - Universidade de São Paulo (USP)false |
dc.title.none.fl_str_mv |
Phaeurus antarcticus and its endophytic fungi: chemical diversity of a hidden pharmacy underneath the Antarctic Ocean Phaeurus antarcticus e seus fungos endofíticos: diversidade química de uma farmácia oculta sob o oceano Antártico |
title |
Phaeurus antarcticus and its endophytic fungi: chemical diversity of a hidden pharmacy underneath the Antarctic Ocean |
spellingShingle |
Phaeurus antarcticus and its endophytic fungi: chemical diversity of a hidden pharmacy underneath the Antarctic Ocean Santos, Gustavo Souza dos Antarctic fungi Antarctic seaweed Antimicrobials Antimicrobianos Atividade imunomoduladora Doenças negligenciadas Fotoproteção Fungos antárticos Immunomodulatory activity Macroalgas antárticas Marine natural products Metabolômica Metabolomics Neglected diseases Photoprotection Produtos naturais marinhos |
title_short |
Phaeurus antarcticus and its endophytic fungi: chemical diversity of a hidden pharmacy underneath the Antarctic Ocean |
title_full |
Phaeurus antarcticus and its endophytic fungi: chemical diversity of a hidden pharmacy underneath the Antarctic Ocean |
title_fullStr |
Phaeurus antarcticus and its endophytic fungi: chemical diversity of a hidden pharmacy underneath the Antarctic Ocean |
title_full_unstemmed |
Phaeurus antarcticus and its endophytic fungi: chemical diversity of a hidden pharmacy underneath the Antarctic Ocean |
title_sort |
Phaeurus antarcticus and its endophytic fungi: chemical diversity of a hidden pharmacy underneath the Antarctic Ocean |
author |
Santos, Gustavo Souza dos |
author_facet |
Santos, Gustavo Souza dos |
author_role |
author |
dc.contributor.none.fl_str_mv |
Debonsi, Hosana Maria Edrada-ebel, Ru Angelie |
dc.contributor.author.fl_str_mv |
Santos, Gustavo Souza dos |
dc.subject.por.fl_str_mv |
Antarctic fungi Antarctic seaweed Antimicrobials Antimicrobianos Atividade imunomoduladora Doenças negligenciadas Fotoproteção Fungos antárticos Immunomodulatory activity Macroalgas antárticas Marine natural products Metabolômica Metabolomics Neglected diseases Photoprotection Produtos naturais marinhos |
topic |
Antarctic fungi Antarctic seaweed Antimicrobials Antimicrobianos Atividade imunomoduladora Doenças negligenciadas Fotoproteção Fungos antárticos Immunomodulatory activity Macroalgas antárticas Marine natural products Metabolômica Metabolomics Neglected diseases Photoprotection Produtos naturais marinhos |
description |
Chapter I: The chemical profile and antibacterial, antiparasitic, and insecticidal activities of the seaweed P. antarcticus were investigated. The hexane extract (HX) and its fractions exhibited selective antibacterial activity against Staphylococcus aureus. Fractions HX-FC and HX-FD showed the highest antiparasitic activity against Leishmania amazonensis and Neospora caninum. The HX extract and the HX-FC fraction presented insecticidal potential against Aedes aegypti larvae. Through GC-MS analysis and the combination of multivariate statistical analyses (OPLS-DA) and the construction of molecular networks (GNPS), it was possible to annotate terpenes, steroids, fatty acids, and alcohols in the bioactive fractions. Chapter II: Using metabolomics techniques (UPLC-HRMS/1H NMR) and multivariate statistical analysis (PCA, OPLS-DA), the spatial variability of secondary metabolites of the seaweed P. antarcticus and the antibiofilm activity of extracts and fractions were evaluated against S. aureus resistant to methicillin-oxacillin (MRSA). The results revealed that the changes in the chemical profile were not site-specific and could be related to different life cycle stages of the collected algae. Porphyrins, terpenes, and carotenoids were annotated as discriminating compounds. Linoleic acid (1) and fucosterol (2) were isolated from the bioactive fractions and showed antibiofilm activity against MRSA. Chapter III: The extract and fractions of the fungus Penicillium purpurogenum were evaluated for antibacterial, antiparasitic, immunomodulatory, and photoprotective activities. The bioguided fractionation led to the isolation of six polyketides: 5,6,8-trihydroxy-4-(1\'-hydroxyethyl) isocoumarin (3), aspergillumarin A (4), aspergillumarin B (5), Berkeleyacetal C (6), sescandelin (7), and vermistatin (8). Compounds 3, 4, 7, and 8 presented photostability and photoprotective activities against UVB-UVA. Compounds 3, 6, 7, and 8 presented immunomodulatory activity by down-regulating the production of reactive oxygen species in PMA-stimulated human neutrophils without cytotoxic effects. Compound 6 presented leishmanicidal activity against amastigotes of L. amazonensis. Chapter IV: The chemical profile (UPLC-HRMS/1H NMR) and antibiofilm activity against MRSA of 21 fungal strains were investigated. Among them, the fractionation of the extract of the fungus Epicoccum nigrum led to the isolation of epicorazines A-B (9-10) and C (12) as well as a new terpenoid (11). Compound 9-12 exhibited antibiofilm activity against MRSA. Among these, compound 11 showed the highest inhibition of pre-biofilm formation and rupture of the formed biofilm. Given the global context, this work sought to obtain new biotechnological products, considering the United Nations Sustainable Development Goals. The results obtained provide new information about the chemotaxonomy and biotechnological potential of Antarctic marine organisms as producers of biomolecules of pharmaceutical interest, emphasizing the importance of bioprospecting for the conservation of understudied organisms. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022-11-29 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://www.teses.usp.br/teses/disponiveis/60/60138/tde-20072023-113231/ |
url |
https://www.teses.usp.br/teses/disponiveis/60/60138/tde-20072023-113231/ |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
|
dc.rights.driver.fl_str_mv |
Liberar o conteúdo para acesso público. info:eu-repo/semantics/openAccess |
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Liberar o conteúdo para acesso público. |
eu_rights_str_mv |
openAccess |
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application/pdf |
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dc.publisher.none.fl_str_mv |
Biblioteca Digitais de Teses e Dissertações da USP |
publisher.none.fl_str_mv |
Biblioteca Digitais de Teses e Dissertações da USP |
dc.source.none.fl_str_mv |
reponame:Biblioteca Digital de Teses e Dissertações da USP instname:Universidade de São Paulo (USP) instacron:USP |
instname_str |
Universidade de São Paulo (USP) |
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USP |
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USP |
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Biblioteca Digital de Teses e Dissertações da USP |
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Biblioteca Digital de Teses e Dissertações da USP |
repository.name.fl_str_mv |
Biblioteca Digital de Teses e Dissertações da USP - Universidade de São Paulo (USP) |
repository.mail.fl_str_mv |
virginia@if.usp.br|| atendimento@aguia.usp.br||virginia@if.usp.br |
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1818598125904855040 |