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Doctoral Thesis
DOI
10.11606/T.75.2017.tde-29092017-174924
Document
Author
Full name
Karen de Jesus Nicácio
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Carlos, 2017
Supervisor
Committee
Berlinck, Roberto Gomes de Souza (President)
Espindola, Laila Salmen
Fiore, Marli de Fatima
Gamboa, Ian Castro
Marsaioli, Anita Jocelyne
Title in Portuguese
Isolamento e identificação de metabólitos produzidos por linhagens de microrganismos do ambiente marinho
Keywords in Portuguese
bactérias
fungos
Metabólitos secundários
Abstract in Portuguese
A investigação de produtos naturais tem sido cada vez mais direcionada para o estudo de microrganismos, com destaque para aqueles do ambiente marinho. Neste trabalho foram estudadas linhagens bacterianas isoladas de tecidos da esponja Arenosclera brasiliensis, como parte de um estudo que tinha o objetivo de encontrar novas moléculas bioativas. O cultivo da linhagem bacteriana Pseudovibrio denitrificans Ab134 permitiu o isolamento e identificação de três compostos derivados de dibromotirosina, a fistularina-3 (26), o ácido verongidoico (27) e a 11-hidroxiaerotionina (28). Outros cinco compostos derivados de dibromotirosina foram detectados, em frações ainda impuras, através de análises por CLUE-qTOF e tiveram suas estruturas propostas de acordo com os íons de fragmentação observados no espectro de EMAR: aerotionina (29), um éster do ácido purpurocerático B (30), purealidina L (31) e aplisinamisina II (32). Este é o primeiro relato da produção dos derivados de dibromotirosina a partir de uma linhagem bacteriana e representa um forte indício de que tais compostos, comumente isolados de esponjas, são na verdade produzidos pela microbiota associada destes animais. O cultivo da linhagem fúngica Biatriospora sp. permitiu o isolamento e identificação de nove compostos diterpênicos da classe das fomactinas, sendo seis deles inéditos. As fomactinas são conhecidas por apresentarem potente atividade como inibidoras de receptores do PAF. As fomactinas S, P, U e I apresentaram bons resultados na inibição da ligação do PAF aos seus receptores. As fomactinas S e P foram também avaliadas em ensaio de re-população tumoral pós irradiação e foram capazes de inibir o fenômeno de re-população em concentração molar equivalente a antagonistas comerciais. Tal resultado sugere que a associação da radioterapia com antagonistas do PAF-R pode ser uma nova e eficiente alternativa terapêutica para inibição do crescimento de tumores.
Title in English
Isolation and identification of metabolites produced by strains of microorganisms from the marine environment
Keywords in English
bacteria
fungi
Secondary metabolites
Abstract in English
Research on natural products is increasingly focusing on the study of microorganisms, especially those from the marine environment. In the present investigation, bacterial strains isolated from tissues of the sponge Arenosclera brasiliensis were studied in order to find new bioactive molecules. Cultivation of the bacterial strain P. denitrificans allowed the isolation and identification of three dibromotyrosine-derived compounds: fistularin-3 (26), verongidoic acid (27) and 11-hydroxyaerothionin (28). Another five dibromotyrosine-derived compounds were detected in still impure fractions by UPLC-qTOF analysis and had their structures proposed according to the fragmentation ions observed in the HRMS spectrum: aerothionin (29), the methyl ester of purpuroceric acid B (30), purealidin L (31) and aplisinamysin II (32). This is the first report of the production of dibromotyrosine derivatives by a bacterial strain and represents a strong indication that such compounds, commonly isolated from sponges, are actually produced by the associated microbiota of these animals. Cultivation of the fungal strain Biatriospora sp. allowed the isolation and identification of nine fomactin diterpenes, six of wich are new. Fomactins are known as inhibitors of PAF receptors. Fomactins S, P, U and I have shown good results in inhibiting the binding of PAF to their receptors. The fomatins S and P were also evaluated in the post-irradiation tumor re-population assay and were able to inhibit the re-population phenomenon at micromolar concentration equivalent to commercial antagonists. Such a result suggests that the association of radiotherapy with PAF-R antagonists may be a new and efficient therapeutic alternative in tumors.
 
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Publishing Date
2017-10-04
 
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