Estudo da inibi??o da monoamina oxidase por novos compostos sint?ticos derivados de cumarina
| Ano de defesa: | 2019 |
|---|---|
| Autor(a) principal: |
Lima, Lin Machado de
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| Orientador(a): | |
| Banca de defesa: | , , , |
| Tipo de documento: | Dissertação |
| Tipo de acesso: | Acesso aberto |
| Idioma: | por |
| Instituição de defesa: |
Universidade Federal Rural do Rio de Janeiro
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| Programa de Pós-Graduação: |
Programa de P?s-Gradua??o em Qu?mica
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| Departamento: |
Instituto de Qu?mica
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| País: |
Brasil
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| Palavras-chave em Português: | |
| Palavras-chave em Inglês: | |
| Área do conhecimento CNPq: | |
| Link de acesso: | https://tede.ufrrj.br/jspui/handle/jspui/5322 |
Resumo: | Monoamine oxidase [EC 1.4.3.4 (MAO)] is an enzyme located in the outer membrane of the mitochondria, which uses flavin adenine dinucleotide (FAD) as a cofactor to catalyze the oxidant conversion of an amine in its corresponding aldehyde, also producing ammonia and hydrogen peroxide. MAO activity regulates the levels of biogenic amines present in tissues, especially in the brain. MAO exists as two proteins: MAO-A and MAO-B. These isoforms were defined primarily by substrate affinities and inhibitor sensitivity. Accordingly, MAO-A oxidizes, preferably, serotonin, melatonin, noradrenaline and adrenaline. MAO-B preferably oxidizes phenylethylamine, an alkaloid from the metabolism of phenylalanine. The ingestion of phenylethylamine promotes the release of dopamine that acts in the brain stimulating euphoria. Concerning the inhibitors, MAO-A is preferentially inhibited by clorgiline. MAO-B is inhibited by deprenyl and pargyline. These inhibitors can be used in the treatment of degenerative brain diseases. Since studies have shown that molecules derived from coumarins achieved excellent results as inhibitors of these enzymes, several new drugs derived from coumarin have been synthesized, which a few are very promising in the treatment of Alzheimer's and Parkinson's diseases. This study aimed to promote in vitro inhibition tests of MAO with new substances derived from coumarin. Among the compounds tested, two of them were shown to be promising as MAO inhibitors of mitochondrial fraction of wistar rat brain, reaching more than 60% inhibition of monoamine oxidase activity. |
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Salles, Cristiane Martins Cardoso deCPF: 035.399.287-90Bastos, Frederico FreireCPF: 082.617.467-76Vieira, Andr? Luiz GomesFernandes, Daniele Corr?aSantos, Andr? Marques dosBastos Neto, Jayme da CunhaCPF: 805.264.627-87http://lattes.cnpq.br/4443098894988565Lima, Lin Machado de2022-01-19T18:51:45Z2019-07-01LIMA, Lin Machado de. Estudo da inibi??o da monoamina oxidase por novos compostos sint?ticos derivados de cumarina. 2019. 33 f. Disserta??o (Mestrado em Qu??mica) - Instituto de Qu??mica, Departamento de Bioqu??mica, Universidade Federal Rural do Rio de Janeiro, Serop?dica, 2019.https://tede.ufrrj.br/jspui/handle/jspui/5322Monoamine oxidase [EC 1.4.3.4 (MAO)] is an enzyme located in the outer membrane of the mitochondria, which uses flavin adenine dinucleotide (FAD) as a cofactor to catalyze the oxidant conversion of an amine in its corresponding aldehyde, also producing ammonia and hydrogen peroxide. MAO activity regulates the levels of biogenic amines present in tissues, especially in the brain. MAO exists as two proteins: MAO-A and MAO-B. These isoforms were defined primarily by substrate affinities and inhibitor sensitivity. Accordingly, MAO-A oxidizes, preferably, serotonin, melatonin, noradrenaline and adrenaline. MAO-B preferably oxidizes phenylethylamine, an alkaloid from the metabolism of phenylalanine. The ingestion of phenylethylamine promotes the release of dopamine that acts in the brain stimulating euphoria. Concerning the inhibitors, MAO-A is preferentially inhibited by clorgiline. MAO-B is inhibited by deprenyl and pargyline. These inhibitors can be used in the treatment of degenerative brain diseases. Since studies have shown that molecules derived from coumarins achieved excellent results as inhibitors of these enzymes, several new drugs derived from coumarin have been synthesized, which a few are very promising in the treatment of Alzheimer's and Parkinson's diseases. This study aimed to promote in vitro inhibition tests of MAO with new substances derived from coumarin. Among the compounds tested, two of them were shown to be promising as MAO inhibitors of mitochondrial fraction of wistar rat brain, reaching more than 60% inhibition of monoamine oxidase activity.A monoamina oxidase [EC 1.4.3.4 (MAO)] ? uma enzima localizada na membrana externa da mitoc?ndria que usa a flavina adenina dinucleot?deo (FAD) como cofator enzim?tico para catalisar a convers?o oxidante de uma amina em seu alde?do correspondente, produzindo tamb?m am?nia e per?xido de hidrog?nio. A atividade das monoamina oxidases regula os n?veis de aminas biog?nicas presentes nos tecidos, principalmente no c?rebro. Monoamina oxidases existem como duas prote?nas: MAO-A e MAO-B. Estas isoformas foram definidas primariamente pelas afinidades por substratos e sensibilidade aos inibidores. Assim, a MAO-A oxida preferencialmente serotonina, melatonina, noradrenalina e adrenalina. A MAO-B oxida preferencialmente a feniletilamina, um alcaloide do metabolismo da fenilalanina. A ingest?o de feniletilamina promove a libera??o de dopamina que atua no c?rebro estimulando euforia. Com rela??o aos inibidores, a MAO-A ? inibida preferencialmente por clorgilina. MAO-B ? inibida por deprenil e por pargilina. Esses inibidores podem ser usados para o tratamento das doen?as degenerativas do c?rebro. Desde que estudos t?m mostrado que mol?culas derivadas de cumarinas obtiveram excelentes resultados como inibidoras destas enzimas, muitas drogas novas derivadas da cumarina v?m sendo sintetizadas, das quais algumas s?o muito promissoras para o tratamento das doen?as de Alzheimer e Parkinson. O alvo desse trabalho foi promover testes de inibi??o in vitro da MAO da fra??o mitocondrial de c?rebro de rato Wistar com novos produtos derivados da cumarina. Dentre os compostos testados, dois deles se mostraram promissores como inibidores da MAO de fra??o mitocondrial de c?rebro de rato wistar, atingindo mais de 60% de inibi??o da atividade da monoamina oxidase.Submitted by Jorge Silva (jorgelmsilva@ufrrj.br) on 2022-01-19T18:51:44Z No. of bitstreams: 1 2019 - Lin Machado de Lima.pdf: 931751 bytes, checksum: b85decb15478a60703cdbcccab374702 (MD5)Made available in DSpace on 2022-01-19T18:51:45Z (GMT). No. of bitstreams: 1 2019 - Lin Machado de Lima.pdf: 931751 bytes, checksum: b85decb15478a60703cdbcccab374702 (MD5) Previous issue date: 2019-07-01CAPES - Coordena??o de Aperfei?oamento de Pessoal de N?vel Superiorapplication/pdfhttps://tede.ufrrj.br/retrieve/67901/2019%20-%20Lin%20Machado%20de%20Lima.pdf.jpgporUniversidade Federal Rural do Rio de JaneiroPrograma de P?s-Gradua??o em Qu?micaUFRRJBrasilInstituto de Qu?mica1.(JPND), E.J.-N.([s.d.]). de JPND Research. Dispon?vel em:?http://www.neurodegenerationresearch.eu/about/what/?. Acesso em maio de 2013. 2.Alzheimer?s association. , de Alzheimer?s Australia. Dispon?vel em:?http://www.fightdementia.org.au/understanding-dementia/section-1-about-dementia.aspx?. Acesso em maio de 2013. 3.ANNAMALAI, B.; WON, J.S.; CHOI, S.; SINGH, I.; SINGH, A.K.. Role of s-nitrosoglutathione mediated mechanisms in tau hyper-phosphorylation. 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Neuroscience, 115, n? 1, 201-211, 2002. 88.ZHU, X.; SU, B.; WANG, X.; SMITH, M.A.; PERRY, G.. Causes of oxidative stress inAlzheimer?s disease. 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| dc.title.por.fl_str_mv |
Estudo da inibi??o da monoamina oxidase por novos compostos sint?ticos derivados de cumarina |
| dc.title.alternative.eng.fl_str_mv |
Study of the inhibition of monoamine oxidase by new synthetic compounds derived from coumarin |
| title |
Estudo da inibi??o da monoamina oxidase por novos compostos sint?ticos derivados de cumarina |
| spellingShingle |
Estudo da inibi??o da monoamina oxidase por novos compostos sint?ticos derivados de cumarina Lima, Lin Machado de Monoamina oxidase Cumarina Inibidores de enzimas Monoamine oxidase Coumarin Enzymes Inhibitors Qu?mica |
| title_short |
Estudo da inibi??o da monoamina oxidase por novos compostos sint?ticos derivados de cumarina |
| title_full |
Estudo da inibi??o da monoamina oxidase por novos compostos sint?ticos derivados de cumarina |
| title_fullStr |
Estudo da inibi??o da monoamina oxidase por novos compostos sint?ticos derivados de cumarina |
| title_full_unstemmed |
Estudo da inibi??o da monoamina oxidase por novos compostos sint?ticos derivados de cumarina |
| title_sort |
Estudo da inibi??o da monoamina oxidase por novos compostos sint?ticos derivados de cumarina |
| author |
Lima, Lin Machado de |
| author_facet |
Lima, Lin Machado de |
| author_role |
author |
| dc.contributor.advisor1.fl_str_mv |
Salles, Cristiane Martins Cardoso de |
| dc.contributor.advisor1ID.fl_str_mv |
CPF: 035.399.287-90 |
| dc.contributor.advisor-co1.fl_str_mv |
Bastos, Frederico Freire |
| dc.contributor.advisor-co1ID.fl_str_mv |
CPF: 082.617.467-76 |
| dc.contributor.referee1.fl_str_mv |
Vieira, Andr? Luiz Gomes |
| dc.contributor.referee2.fl_str_mv |
Fernandes, Daniele Corr?a |
| dc.contributor.referee3.fl_str_mv |
Santos, Andr? Marques dos |
| dc.contributor.referee4.fl_str_mv |
Bastos Neto, Jayme da Cunha |
| dc.contributor.authorID.fl_str_mv |
CPF: 805.264.627-87 |
| dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/4443098894988565 |
| dc.contributor.author.fl_str_mv |
Lima, Lin Machado de |
| contributor_str_mv |
Salles, Cristiane Martins Cardoso de Bastos, Frederico Freire Vieira, Andr? Luiz Gomes Fernandes, Daniele Corr?a Santos, Andr? Marques dos Bastos Neto, Jayme da Cunha |
| dc.subject.por.fl_str_mv |
Monoamina oxidase Cumarina Inibidores de enzimas |
| topic |
Monoamina oxidase Cumarina Inibidores de enzimas Monoamine oxidase Coumarin Enzymes Inhibitors Qu?mica |
| dc.subject.eng.fl_str_mv |
Monoamine oxidase Coumarin Enzymes Inhibitors |
| dc.subject.cnpq.fl_str_mv |
Qu?mica |
| description |
Monoamine oxidase [EC 1.4.3.4 (MAO)] is an enzyme located in the outer membrane of the mitochondria, which uses flavin adenine dinucleotide (FAD) as a cofactor to catalyze the oxidant conversion of an amine in its corresponding aldehyde, also producing ammonia and hydrogen peroxide. MAO activity regulates the levels of biogenic amines present in tissues, especially in the brain. MAO exists as two proteins: MAO-A and MAO-B. These isoforms were defined primarily by substrate affinities and inhibitor sensitivity. Accordingly, MAO-A oxidizes, preferably, serotonin, melatonin, noradrenaline and adrenaline. MAO-B preferably oxidizes phenylethylamine, an alkaloid from the metabolism of phenylalanine. The ingestion of phenylethylamine promotes the release of dopamine that acts in the brain stimulating euphoria. Concerning the inhibitors, MAO-A is preferentially inhibited by clorgiline. MAO-B is inhibited by deprenyl and pargyline. These inhibitors can be used in the treatment of degenerative brain diseases. Since studies have shown that molecules derived from coumarins achieved excellent results as inhibitors of these enzymes, several new drugs derived from coumarin have been synthesized, which a few are very promising in the treatment of Alzheimer's and Parkinson's diseases. This study aimed to promote in vitro inhibition tests of MAO with new substances derived from coumarin. Among the compounds tested, two of them were shown to be promising as MAO inhibitors of mitochondrial fraction of wistar rat brain, reaching more than 60% inhibition of monoamine oxidase activity. |
| publishDate |
2019 |
| dc.date.issued.fl_str_mv |
2019-07-01 |
| dc.date.accessioned.fl_str_mv |
2022-01-19T18:51:45Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
| format |
masterThesis |
| status_str |
publishedVersion |
| dc.identifier.citation.fl_str_mv |
LIMA, Lin Machado de. Estudo da inibi??o da monoamina oxidase por novos compostos sint?ticos derivados de cumarina. 2019. 33 f. Disserta??o (Mestrado em Qu??mica) - Instituto de Qu??mica, Departamento de Bioqu??mica, Universidade Federal Rural do Rio de Janeiro, Serop?dica, 2019. |
| dc.identifier.uri.fl_str_mv |
https://tede.ufrrj.br/jspui/handle/jspui/5322 |
| identifier_str_mv |
LIMA, Lin Machado de. Estudo da inibi??o da monoamina oxidase por novos compostos sint?ticos derivados de cumarina. 2019. 33 f. Disserta??o (Mestrado em Qu??mica) - Instituto de Qu??mica, Departamento de Bioqu??mica, Universidade Federal Rural do Rio de Janeiro, Serop?dica, 2019. |
| url |
https://tede.ufrrj.br/jspui/handle/jspui/5322 |
| dc.language.iso.fl_str_mv |
por |
| language |
por |
| dc.relation.references.por.fl_str_mv |
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