Avaliação dos efeitos farmacológico e toxicológico de 4- organocalcogeno-isoquinolinas
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/11226 |
Resumo: | Monoamine oxidase (MAO) is a target enzyme in the treatment of several pathologies, being that new molecules which inhibit of a selective, potent and reversible manner their isoforms and without adverse effects are searched. In this way, the first manuscript of this dissertation evaluated the in vitro inhibitory potential of the 4-organochalcogen-isoquinolines on cerebral MAO-A and B activities, elucidating their kinetics profile and the interaction compound x enzyme. The results demonstrated that all compounds were selective inhibitors of MAO-B, being compound 3-phenyl-4-(selenophenyl) isoquinoline the most potent. The kinetics profile revealed a mixed and reversible inhibition of enzyme, consistent to the results of molecular docking. It is known that both organic selenium compounds and isoquinolines are linked to pro-oxidants situations, thus, it was investigated the in vitro effect of 4-organoseleno-isoquinolines on cerebral activities of the enzymes δ- aminolevulinate dehydratase (δ-ALA-D) e Na+, K+-ATPase, which have easily oxidized cysteine residues. Data demonstrated that compounds substituted with chloro, fluoro and trifluoromethyl in the aromatic ring bonded to the selenium atom of compound 3-phenyl-4-(selenophenyl) isoquinoline inhibited both sulfhydryl enzymes, which was not observed in the compound substituted with methyl and in a nonsubstituted compound. Furthermore, since the inhibition of enzymes δ-ALA-D and Na+, K+-ATPase was restored by dithiothreitol it is possible to propose the oxidation of cysteine residues by compounds. The selective and reversible inhibition of MAO-B and the low toxicological potential demonstrated by compound 3-phenyl-4- (selenophenyl) isoquinoline become this compound a candidate for more studies, which aim this enzyme as a therapeutic target. |
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2015-02-272015-02-272014-03-12SAMPAIO, Tuane Bazanella. EVALUATION OF PHARMACOLOGYC AND TOXICOLOGYC EFFECTS OF 4-ORGANOCHALCOGEN-ISOQUINOLINES. 2014. 84 f. Dissertação (Mestrado em Ciências Biológicas) - Universidade Federal de Santa Maria, Santa Maria, 2014.http://repositorio.ufsm.br/handle/1/11226Monoamine oxidase (MAO) is a target enzyme in the treatment of several pathologies, being that new molecules which inhibit of a selective, potent and reversible manner their isoforms and without adverse effects are searched. In this way, the first manuscript of this dissertation evaluated the in vitro inhibitory potential of the 4-organochalcogen-isoquinolines on cerebral MAO-A and B activities, elucidating their kinetics profile and the interaction compound x enzyme. The results demonstrated that all compounds were selective inhibitors of MAO-B, being compound 3-phenyl-4-(selenophenyl) isoquinoline the most potent. The kinetics profile revealed a mixed and reversible inhibition of enzyme, consistent to the results of molecular docking. It is known that both organic selenium compounds and isoquinolines are linked to pro-oxidants situations, thus, it was investigated the in vitro effect of 4-organoseleno-isoquinolines on cerebral activities of the enzymes δ- aminolevulinate dehydratase (δ-ALA-D) e Na+, K+-ATPase, which have easily oxidized cysteine residues. Data demonstrated that compounds substituted with chloro, fluoro and trifluoromethyl in the aromatic ring bonded to the selenium atom of compound 3-phenyl-4-(selenophenyl) isoquinoline inhibited both sulfhydryl enzymes, which was not observed in the compound substituted with methyl and in a nonsubstituted compound. Furthermore, since the inhibition of enzymes δ-ALA-D and Na+, K+-ATPase was restored by dithiothreitol it is possible to propose the oxidation of cysteine residues by compounds. The selective and reversible inhibition of MAO-B and the low toxicological potential demonstrated by compound 3-phenyl-4- (selenophenyl) isoquinoline become this compound a candidate for more studies, which aim this enzyme as a therapeutic target.A monoamina oxidase (MAO) é uma enzima alvo no tratamento de diversas patologias, sendo que novas moléculas que a inibam de maneira seletiva, potente, reversível, e ausente de efeitos adversos suas isoformas são procuradas. Neste sentido, o primeiro manuscrito desta dissertação avaliou o potencial inibitório dos 4- organocalcogeno-isoquinolinas na atividade cerebral da MAO-A e B in vitro, elucidando seus perfis cinéticos e a interação composto e enzima. Os resultados demonstram que todos os compostos apresentam inibição seletiva da MAO-B, sendo o composto 3-fenil-4-(selenofenil) isoquinolina o mais potente. O perfil cinético revelou inibição do tipo mista e reversível da enzima, coerente aos resultados do docking molecular. Sabe-se que tanto compostos orgânicos de selênio quanto isoquinolinas relacionam-se a situações pró-oxidantes, deste modo, investigou-se o efeito in vitro dos 4-organoseleno-isoquinolinas na atividade cerebral das enzimas δ- aminolevulinato dehidratase (δ-ALA-D) e Na+, K+-ATPase, as quais possuem resíduos de cisteína facilmente oxidáveis. Os dados demonstram que os compostos substituídos com cloro, flúor e trifluormetil no anel aromático ligado ao átomo de Se do composto 3-fenil-4-(selenofenil) isoquinolina inibem ambas as enzimas sulfidrílicas, o que não foi observado com o composto substituído com metil e com o composto não substituído. Além disso, visto que a inibição das enzimas δ-ALA-D e Na+, K+-ATPase foi revertida por ditiotreitol é possível propor o envolvimento da oxidação dos resíduos de cisteína pelos compostos. Devido à inibição seletiva e reversível da MAO-B e ao baixo potencial toxicológico demonstrado, o composto 3- fenil-4-(selenofenil) isoquinolina torna-se um candidato a mais estudos que possuam esta enzima como alvo terapêutico.Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorapplication/pdfporUniversidade Federal de Santa MariaPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaUFSMBRBioquímicaδ-ALA-DIsoquinolinaMAONa+, K+-ATPaseSelênioIsoquinolineSeleniumCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAAvaliação dos efeitos farmacológico e toxicológico de 4- organocalcogeno-isoquinolinasEvaluation of pharmacologyc and toxicologyc effects of 4-organochalcogen-isoquinolinesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisNogueira, Cristina Waynehttp://lattes.cnpq.br/2877042401245169Fachinetto, Roseleihttp://lattes.cnpq.br/7203076675431306Lugokenski, Thiago Henriquehttp://lattes.cnpq.br/4211206301954369http://lattes.cnpq.br/5691644332678684Sampaio, Tuane Bazanella2008000000024005003005003000186436d-f662-4a5e-b36e-8c8ab8e10bf85d4abff3-8b03-463e-98b9-bbc4fdb2c231d4a64262-0e7e-45c5-910e-0b0aee907c1058176442-29ed-4b85-b53a-93fdf60815f5info:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALSAMPAIO, TUANE BAZANELLA.pdfapplication/pdf2945520http://repositorio.ufsm.br/bitstream/1/11226/1/SAMPAIO%2c%20TUANE%20BAZANELLA.pdf34e24e97d3e475e948e0601424df8776MD51TEXTSAMPAIO, TUANE BAZANELLA.pdf.txtSAMPAIO, TUANE BAZANELLA.pdf.txtExtracted texttext/plain155090http://repositorio.ufsm.br/bitstream/1/11226/2/SAMPAIO%2c%20TUANE%20BAZANELLA.pdf.txt5a8b2bd44291ebc7b147b59129081f43MD52THUMBNAILSAMPAIO, TUANE BAZANELLA.pdf.jpgSAMPAIO, TUANE BAZANELLA.pdf.jpgIM Thumbnailimage/jpeg4950http://repositorio.ufsm.br/bitstream/1/11226/3/SAMPAIO%2c%20TUANE%20BAZANELLA.pdf.jpgb7b8700a689db09034939f0e45e94c18MD531/112262022-02-02 08:41:08.986oai:repositorio.ufsm.br:1/11226Repositório Institucionalhttp://repositorio.ufsm.br/PUBhttp://repositorio.ufsm.br/oai/requestopendoar:39132022-02-02T11:41:08Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
Avaliação dos efeitos farmacológico e toxicológico de 4- organocalcogeno-isoquinolinas |
dc.title.alternative.eng.fl_str_mv |
Evaluation of pharmacologyc and toxicologyc effects of 4-organochalcogen-isoquinolines |
title |
Avaliação dos efeitos farmacológico e toxicológico de 4- organocalcogeno-isoquinolinas |
spellingShingle |
Avaliação dos efeitos farmacológico e toxicológico de 4- organocalcogeno-isoquinolinas Sampaio, Tuane Bazanella δ-ALA-D Isoquinolina MAO Na+, K+-ATPase Selênio Isoquinoline Selenium CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
title_short |
Avaliação dos efeitos farmacológico e toxicológico de 4- organocalcogeno-isoquinolinas |
title_full |
Avaliação dos efeitos farmacológico e toxicológico de 4- organocalcogeno-isoquinolinas |
title_fullStr |
Avaliação dos efeitos farmacológico e toxicológico de 4- organocalcogeno-isoquinolinas |
title_full_unstemmed |
Avaliação dos efeitos farmacológico e toxicológico de 4- organocalcogeno-isoquinolinas |
title_sort |
Avaliação dos efeitos farmacológico e toxicológico de 4- organocalcogeno-isoquinolinas |
author |
Sampaio, Tuane Bazanella |
author_facet |
Sampaio, Tuane Bazanella |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Nogueira, Cristina Wayne |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/2877042401245169 |
dc.contributor.referee1.fl_str_mv |
Fachinetto, Roselei |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/7203076675431306 |
dc.contributor.referee2.fl_str_mv |
Lugokenski, Thiago Henrique |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/4211206301954369 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/5691644332678684 |
dc.contributor.author.fl_str_mv |
Sampaio, Tuane Bazanella |
contributor_str_mv |
Nogueira, Cristina Wayne Fachinetto, Roselei Lugokenski, Thiago Henrique |
dc.subject.por.fl_str_mv |
δ-ALA-D Isoquinolina MAO Na+, K+-ATPase Selênio |
topic |
δ-ALA-D Isoquinolina MAO Na+, K+-ATPase Selênio Isoquinoline Selenium CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
dc.subject.eng.fl_str_mv |
Isoquinoline Selenium |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
description |
Monoamine oxidase (MAO) is a target enzyme in the treatment of several pathologies, being that new molecules which inhibit of a selective, potent and reversible manner their isoforms and without adverse effects are searched. In this way, the first manuscript of this dissertation evaluated the in vitro inhibitory potential of the 4-organochalcogen-isoquinolines on cerebral MAO-A and B activities, elucidating their kinetics profile and the interaction compound x enzyme. The results demonstrated that all compounds were selective inhibitors of MAO-B, being compound 3-phenyl-4-(selenophenyl) isoquinoline the most potent. The kinetics profile revealed a mixed and reversible inhibition of enzyme, consistent to the results of molecular docking. It is known that both organic selenium compounds and isoquinolines are linked to pro-oxidants situations, thus, it was investigated the in vitro effect of 4-organoseleno-isoquinolines on cerebral activities of the enzymes δ- aminolevulinate dehydratase (δ-ALA-D) e Na+, K+-ATPase, which have easily oxidized cysteine residues. Data demonstrated that compounds substituted with chloro, fluoro and trifluoromethyl in the aromatic ring bonded to the selenium atom of compound 3-phenyl-4-(selenophenyl) isoquinoline inhibited both sulfhydryl enzymes, which was not observed in the compound substituted with methyl and in a nonsubstituted compound. Furthermore, since the inhibition of enzymes δ-ALA-D and Na+, K+-ATPase was restored by dithiothreitol it is possible to propose the oxidation of cysteine residues by compounds. The selective and reversible inhibition of MAO-B and the low toxicological potential demonstrated by compound 3-phenyl-4- (selenophenyl) isoquinoline become this compound a candidate for more studies, which aim this enzyme as a therapeutic target. |
publishDate |
2014 |
dc.date.issued.fl_str_mv |
2014-03-12 |
dc.date.accessioned.fl_str_mv |
2015-02-27 |
dc.date.available.fl_str_mv |
2015-02-27 |
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 |
SAMPAIO, Tuane Bazanella. EVALUATION OF PHARMACOLOGYC AND TOXICOLOGYC EFFECTS OF 4-ORGANOCHALCOGEN-ISOQUINOLINES. 2014. 84 f. Dissertação (Mestrado em Ciências Biológicas) - Universidade Federal de Santa Maria, Santa Maria, 2014. |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/11226 |
identifier_str_mv |
SAMPAIO, Tuane Bazanella. EVALUATION OF PHARMACOLOGYC AND TOXICOLOGYC EFFECTS OF 4-ORGANOCHALCOGEN-ISOQUINOLINES. 2014. 84 f. Dissertação (Mestrado em Ciências Biológicas) - Universidade Federal de Santa Maria, Santa Maria, 2014. |
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http://repositorio.ufsm.br/handle/1/11226 |
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