Estudo da inibição da monoamina oxidase por novos compostos sintéticos derivados de cumarina
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| Data de Publicação: | 2019 |
| Tipo de documento: | Dissertação |
| Idioma: | por |
| Título da fonte: | Biblioteca Digital de Teses e Dissertações da UFRRJ |
| Texto Completo: | https://rima.ufrrj.br/jspui/handle/20.500.14407/14601 |
Resumo: | A monoamina oxidase [EC 1.4.3.4 (MAO)] é uma enzima localizada na membrana externa da mitocôndria que usa a flavina adenina dinucleotídeo (FAD) como cofator enzimático para catalisar a conversão oxidante de uma amina em seu aldeído correspondente, produzindo também amônia e peróxido de hidrogênio. A atividade das monoamina oxidases regula os níveis de aminas biogênicas presentes nos tecidos, principalmente no cérebro. Monoamina oxidases existem como duas proteínas: 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 ingestão de feniletilamina promove a liberação de dopamina que atua no cérebro estimulando euforia. Com relação aos inibidores, a MAO-A é inibida preferencialmente por clorgilina. MAO-B é inibida por deprenil e por pargilina. Esses inibidores podem ser usados para o tratamento das doenças degenerativas do cérebro. Desde que estudos têm mostrado que moléculas derivadas de cumarinas obtiveram excelentes resultados como inibidoras destas enzimas, muitas drogas novas derivadas da cumarina vêm sendo sintetizadas, das quais algumas são muito promissoras para o tratamento das doenças de Alzheimer e Parkinson. O alvo desse trabalho foi promover testes de inibição in vitro da MAO da fração mitocondrial de cérebro de rato Wistar com novos produtos derivados da cumarina. Dentre os compostos testados, dois deles se mostraram promissores como inibidores da MAO de fração mitocondrial de cérebro de rato wistar, atingindo mais de 60% de inibição da atividade da monoamina oxidase. |
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Lima, Lin Machado deSalles, Cristiane Martins Cardoso deCPF: 035.399.287-90Bastos, Frederico FreireCPF: 082.617.467-76Vieira, André Luiz GomesFernandes, Daniele CorrêaSantos, André Marques dosBastos Neto, Jayme da CunhaCPF: 805.264.627-87http://lattes.cnpq.br/44430988949885652023-12-22T03:03:24Z2023-12-22T03:03:24Z2019-07-01LIMA, Lin Machado de. Estudo da inibição da monoamina oxidase por novos compostos sintéticos derivados de cumarina. 2019. 33 f. Dissertação (Mestrado em Química) - Instituto de Química, Departamento de Bioquímica, Universidade Federal Rural do Rio de Janeiro, Seropédica, 2019.https://rima.ufrrj.br/jspui/handle/20.500.14407/14601A monoamina oxidase [EC 1.4.3.4 (MAO)] é uma enzima localizada na membrana externa da mitocôndria que usa a flavina adenina dinucleotídeo (FAD) como cofator enzimático para catalisar a conversão oxidante de uma amina em seu aldeído correspondente, produzindo também amônia e peróxido de hidrogênio. A atividade das monoamina oxidases regula os níveis de aminas biogênicas presentes nos tecidos, principalmente no cérebro. Monoamina oxidases existem como duas proteínas: 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 ingestão de feniletilamina promove a liberação de dopamina que atua no cérebro estimulando euforia. Com relação aos inibidores, a MAO-A é inibida preferencialmente por clorgilina. MAO-B é inibida por deprenil e por pargilina. Esses inibidores podem ser usados para o tratamento das doenças degenerativas do cérebro. Desde que estudos têm mostrado que moléculas derivadas de cumarinas obtiveram excelentes resultados como inibidoras destas enzimas, muitas drogas novas derivadas da cumarina vêm sendo sintetizadas, das quais algumas são muito promissoras para o tratamento das doenças de Alzheimer e Parkinson. O alvo desse trabalho foi promover testes de inibição in vitro da MAO da fração mitocondrial de cérebro de rato Wistar com novos produtos derivados da cumarina. Dentre os compostos testados, dois deles se mostraram promissores como inibidores da MAO de fração mitocondrial de cérebro de rato wistar, atingindo mais de 60% de inibição da atividade da monoamina oxidase.CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorMonoamine 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.application/pdfporUniversidade Federal Rural do Rio de JaneiroPrograma de Pós-Graduação em QuímicaUFRRJBrasilInstituto de QuímicaMonoamina oxidaseCumarinaInibidores de enzimasMonoamine oxidaseCoumarinEnzymes InhibitorsQuímicaEstudo da inibição da monoamina oxidase por novos compostos sintéticos derivados de cumarinaStudy of the inhibition of monoamine oxidase by new synthetic compounds derived from coumarininfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesis1.(JPND), E.J.-N.([s.d.]). de JPND Research. Disponível em:˂http://www.neurodegenerationresearch.eu/about/what/˃. Acesso em maio de 2013. 2.Alzheimer’s association. , de Alzheimer’s Australia. Disponível em:˂http://www.fightdementia.org.au/understanding-dementia/section-1-about-dementia.aspx˃. 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Journal of the Neurological Sciences, 57, nº 2-3, 407-417,1982. 83.WISHIK, C.M.; NOVAK, M.; EDWARDS, P.C.; KLUG, A.; TICHELAAR, W.;CROWTHER, R.A.. Proc. Natl.Acad. Sci. U.S.A., 85, 4884, 1988. 84.YANG, D.S.; McLAURIN, J.; QIN,K.; WESTAWAY, D.; FRASER, P.E.. Examining thezinc binding site of the amyloid-beta peptide. European Journal Biochemistry, 267, nº22, 6692-6698, 2000. 85.YOUDIM, M.B.; BAKHLE, Y.S.. Monoamine oxidase: isoforms and inhibitors inParkinson’s disease and depressive illness. British Journal Pharmacology, 147, 287-296,2006. 86.YOUDIM, M.B.; WEINSTOCK, M.. Therapeutic applications of selective and non-selective inhibitors of monoamine oxidase A and B that do not cause significant tyraminepotentiation. Neurotoxicology, 25, nº 1-2, 243-250, 2004. 87.ZHENG, W.H.; BASTIANETTO, S.; MENNICKEN, F.; MA, W.; KAR, S.. Amyloid betapeptide induces tau phosphorylation and loss of cholinergic neurons in rat primary septalcultures. Neuroscience, 115, nº 1, 201-211, 2002. 88.ZHU, X.; SU, B.; WANG, X.; SMITH, M.A.; PERRY, G.. Causes of oxidative stress inAlzheimer’s disease. Cellular and Molecular Life Sciences, 64, nº 17, 2202-2210, 2007.https://tede.ufrrj.br/retrieve/67901/2019%20-%20Lin%20Machado%20de%20Lima.pdf.jpghttps://tede.ufrrj.br/jspui/handle/jspui/5322Submitted 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). 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| dc.title.por.fl_str_mv |
Estudo da inibição da monoamina oxidase por novos compostos sintéticos 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 inibição da monoamina oxidase por novos compostos sintéticos derivados de cumarina |
| spellingShingle |
Estudo da inibição da monoamina oxidase por novos compostos sintéticos derivados de cumarina Lima, Lin Machado de Monoamina oxidase Cumarina Inibidores de enzimas Monoamine oxidase Coumarin Enzymes Inhibitors Química |
| title_short |
Estudo da inibição da monoamina oxidase por novos compostos sintéticos derivados de cumarina |
| title_full |
Estudo da inibição da monoamina oxidase por novos compostos sintéticos derivados de cumarina |
| title_fullStr |
Estudo da inibição da monoamina oxidase por novos compostos sintéticos derivados de cumarina |
| title_full_unstemmed |
Estudo da inibição da monoamina oxidase por novos compostos sintéticos derivados de cumarina |
| title_sort |
Estudo da inibição da monoamina oxidase por novos compostos sintéticos derivados de cumarina |
| author |
Lima, Lin Machado de |
| author_facet |
Lima, Lin Machado de |
| author_role |
author |
| dc.contributor.author.fl_str_mv |
Lima, Lin Machado de |
| 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, André Luiz Gomes |
| dc.contributor.referee2.fl_str_mv |
Fernandes, Daniele Corrêa |
| dc.contributor.referee3.fl_str_mv |
Santos, André 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 |
| contributor_str_mv |
Salles, Cristiane Martins Cardoso de Bastos, Frederico Freire Vieira, André Luiz Gomes Fernandes, Daniele Corrêa Santos, André 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 Química |
| dc.subject.eng.fl_str_mv |
Monoamine oxidase Coumarin Enzymes Inhibitors |
| dc.subject.cnpq.fl_str_mv |
Química |
| description |
A monoamina oxidase [EC 1.4.3.4 (MAO)] é uma enzima localizada na membrana externa da mitocôndria que usa a flavina adenina dinucleotídeo (FAD) como cofator enzimático para catalisar a conversão oxidante de uma amina em seu aldeído correspondente, produzindo também amônia e peróxido de hidrogênio. A atividade das monoamina oxidases regula os níveis de aminas biogênicas presentes nos tecidos, principalmente no cérebro. Monoamina oxidases existem como duas proteínas: 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 ingestão de feniletilamina promove a liberação de dopamina que atua no cérebro estimulando euforia. Com relação aos inibidores, a MAO-A é inibida preferencialmente por clorgilina. MAO-B é inibida por deprenil e por pargilina. Esses inibidores podem ser usados para o tratamento das doenças degenerativas do cérebro. Desde que estudos têm mostrado que moléculas derivadas de cumarinas obtiveram excelentes resultados como inibidoras destas enzimas, muitas drogas novas derivadas da cumarina vêm sendo sintetizadas, das quais algumas são muito promissoras para o tratamento das doenças de Alzheimer e Parkinson. O alvo desse trabalho foi promover testes de inibição in vitro da MAO da fração mitocondrial de cérebro de rato Wistar com novos produtos derivados da cumarina. Dentre os compostos testados, dois deles se mostraram promissores como inibidores da MAO de fração mitocondrial de cérebro de rato wistar, atingindo mais de 60% de inibição da atividade da monoamina oxidase. |
| publishDate |
2019 |
| dc.date.issued.fl_str_mv |
2019-07-01 |
| dc.date.accessioned.fl_str_mv |
2023-12-22T03:03:24Z |
| dc.date.available.fl_str_mv |
2023-12-22T03:03:24Z |
| 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 inibição da monoamina oxidase por novos compostos sintéticos derivados de cumarina. 2019. 33 f. Dissertação (Mestrado em Química) - Instituto de Química, Departamento de Bioquímica, Universidade Federal Rural do Rio de Janeiro, Seropédica, 2019. |
| dc.identifier.uri.fl_str_mv |
https://rima.ufrrj.br/jspui/handle/20.500.14407/14601 |
| identifier_str_mv |
LIMA, Lin Machado de. Estudo da inibição da monoamina oxidase por novos compostos sintéticos derivados de cumarina. 2019. 33 f. Dissertação (Mestrado em Química) - Instituto de Química, Departamento de Bioquímica, Universidade Federal Rural do Rio de Janeiro, Seropédica, 2019. |
| url |
https://rima.ufrrj.br/jspui/handle/20.500.14407/14601 |
| dc.language.iso.fl_str_mv |
por |
| language |
por |
| dc.relation.references.por.fl_str_mv |
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