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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Avaliação dos efeitos farmacológico e toxicológico de 4- organocalcogeno-isoquinolinasEvaluation of pharmacologyc and toxicologyc effects of 4-organochalcogen-isoquinolinesδ-ALA-DIsoquinolinaMAONa+, K+-ATPaseSelênioIsoquinolineSeleniumCNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICAMonoamine 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.Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorA 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.Universidade Federal de Santa MariaBRBioquímicaUFSMPrograma de Pós-Graduação em Ciências Biológicas: Bioquímica ToxicológicaNogueira, Cristina Waynehttp://lattes.cnpq.br/2877042401245169Fachinetto, Roseleihttp://lattes.cnpq.br/7203076675431306Lugokenski, Thiago Henriquehttp://lattes.cnpq.br/4211206301954369Sampaio, Tuane Bazanella2015-02-272015-02-272014-03-12info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfapplication/pdfSAMPAIO, 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/1/11226porinfo:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2022-02-02T11:41:08Zoai:repositorio.ufsm.br:1/11226Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2022-02-02T11:41:08Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Avaliação dos efeitos farmacológico e toxicológico de 4- organocalcogeno-isoquinolinas 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.none.fl_str_mv |
Nogueira, Cristina Wayne http://lattes.cnpq.br/2877042401245169 Fachinetto, Roselei http://lattes.cnpq.br/7203076675431306 Lugokenski, Thiago Henrique http://lattes.cnpq.br/4211206301954369 |
dc.contributor.author.fl_str_mv |
Sampaio, Tuane Bazanella |
dc.subject.por.fl_str_mv |
δ-ALA-D Isoquinolina MAO Na+, K+-ATPase Selênio Isoquinoline Selenium CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA |
topic |
δ-ALA-D Isoquinolina MAO Na+, K+-ATPase Selênio Isoquinoline Selenium 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.none.fl_str_mv |
2014-03-12 2015-02-27 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.uri.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. 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. |
url |
http://repositorio.ufsm.br/handle/1/11226 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria BR Bioquímica UFSM Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria BR Bioquímica UFSM Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica |
dc.source.none.fl_str_mv |
reponame:Manancial - Repositório Digital da UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Manancial - Repositório Digital da UFSM |
collection |
Manancial - Repositório Digital da UFSM |
repository.name.fl_str_mv |
Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
_version_ |
1805922067596443648 |