Phaeurus antarcticus and its endophytic fungi: chemical diversity of a hidden pharmacy underneath the Antarctic Ocean

Detalhes bibliográficos
Autor(a) principal: Santos, Gustavo Souza dos
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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spelling 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:USPReter o conteúdo por motivos de patente, publicação e/ou direitos autoriais.info:eu-repo/semantics/openAccesseng2023-08-21T17:03:45Zoai: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:27212023-08-21T17:03:45Biblioteca 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
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