Síntese e correlação entre a estrutura e a atividade leishmanicida de novas amidas estiril-substituídas
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| Data de Publicação: | 2010 |
| Tipo de documento: | Tese |
| Idioma: | por |
| Título da fonte: | Biblioteca Digital de Teses e Dissertações da UFRRJ |
| Texto Completo: | https://rima.ufrrj.br/jspui/handle/20.500.14407/10204 |
Resumo: | Este trabalho relata a preparação de 25 estiril-amidas das quais 8 são inéditas, obtidas através da reação de substituição nucleofílica, via formação do cloreto de ácido, dos ácidos estiril-substituídos com os nucleófilos benzilamina, fenetilamina, 3,4-dimetoxifenetilamina, 3,4-metilenodioxifenetilamina em bons rendimentos. Também foram obtidos derivados N-estiril-N,N’-diciclo-hexil-uréias, via reação de acoplamento com a DCC. Além disso, foram preparados 5 compostos derivados da piperina, amida alcaloidal majoritária de Piper nigrum, sendo 4 deles inéditos na literatura. As técnicas espectroscópicas de IV e RMN de 1H e 13C foram utilizadas para caracterizar os produtos obtidos. Averiguou-se a biodisponibilidade em meio aquoso para os ensaios in vitro das estiril-amidas substituídas em três tipos de veículos (SME, PVP e -CD). Foi realizado, também o estudo da atividade citotóxica das estiril-amidas substituídas frente à forma promastigota de Leishmania amazonensis e às células de macrófagos de camundongo, além da inibição enzimática frente a DNA topoisomerase II- Os ensaios leishmanicidas mostraram que a série estiril-5’-6’-dimetoxifenetilamidas foi a mais citotóxica, apresentando uma maior seletividade diante dos macrófagos. As séries das estiril-benzil e fenetil-amidas apresentaram correlações lineares entre os valores de logP e os % de inibição frente a L. amazonensis na concentração de 50M. Pôde-se observar que, de maneira geral, os veículos CD e PVP contribuíram para a biodisponibilização das amidas independentemente do efeito eletrônico do substituinte. As estiril-amidas, em sua grande maioria, inibiram a atividade enzimática da topoisomerase II-. |
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Pissinate, KeniaLima, Aurea Echevarria Aznar Neveshttp://lattes.cnpq.br/1879077396134052Lima, Marco Edilson Freire deMaciel, Maria Aparecida M.Lima, Débora Decote Ricardo deOliveira, Mácia Cristina deLima, Célio Freire deCastro, Rosane Norahttp://lattes.cnpq.br/85129596425003782023-12-21T18:59:00Z2023-12-21T18:59:00Z2010-08-27Pissinate, Kenia. Síntese e correlação entre a estrutura e a atividade leishmanicida de novas amidas estiril-substituídas. 2010. 160 f. Tese (Programa de Pós-Graduação em Química) - Universidade Federal Rural do Rio de Janeiro, Seropédica.https://rima.ufrrj.br/jspui/handle/20.500.14407/10204Este trabalho relata a preparação de 25 estiril-amidas das quais 8 são inéditas, obtidas através da reação de substituição nucleofílica, via formação do cloreto de ácido, dos ácidos estiril-substituídos com os nucleófilos benzilamina, fenetilamina, 3,4-dimetoxifenetilamina, 3,4-metilenodioxifenetilamina em bons rendimentos. Também foram obtidos derivados N-estiril-N,N’-diciclo-hexil-uréias, via reação de acoplamento com a DCC. Além disso, foram preparados 5 compostos derivados da piperina, amida alcaloidal majoritária de Piper nigrum, sendo 4 deles inéditos na literatura. As técnicas espectroscópicas de IV e RMN de 1H e 13C foram utilizadas para caracterizar os produtos obtidos. Averiguou-se a biodisponibilidade em meio aquoso para os ensaios in vitro das estiril-amidas substituídas em três tipos de veículos (SME, PVP e -CD). Foi realizado, também o estudo da atividade citotóxica das estiril-amidas substituídas frente à forma promastigota de Leishmania amazonensis e às células de macrófagos de camundongo, além da inibição enzimática frente a DNA topoisomerase II- Os ensaios leishmanicidas mostraram que a série estiril-5’-6’-dimetoxifenetilamidas foi a mais citotóxica, apresentando uma maior seletividade diante dos macrófagos. As séries das estiril-benzil e fenetil-amidas apresentaram correlações lineares entre os valores de logP e os % de inibição frente a L. amazonensis na concentração de 50M. Pôde-se observar que, de maneira geral, os veículos CD e PVP contribuíram para a biodisponibilização das amidas independentemente do efeito eletrônico do substituinte. As estiril-amidas, em sua grande maioria, inibiram a atividade enzimática da topoisomerase II-.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, CAPES, Brasil.In this work describes the preparation of styryl-25 amides of which eight are new. The amides were obtained in good yields, by nucleophilic substitution reaction through formation of acid chlorides, by reacting styryl-substituted acids with the nucleophiles benzylamine, phenethylamine, 1,3-benzodioxolphenethylamine and 3,4-dimethoxiphenethylamine. Derivatives N-styryl-N,N'-dicyclo-hexyl-ureas were also obtained by coupling reaction with DCC. In addition, five compounds derivated from piperine, amide alkaloidal majority of Piper nigrum, were prepared, 4 of them new. The spectroscopic techniques IV and RMN 1H and 13C were used to characterize the products obtained. The bioavailability in aqueous medium for in vitro tests of styryl-substituted amides in three types of vehicles (EMS, PVP and -CD) was tested. The cytotoxicity of styryl-substituted amides for the promastigote form of Leishmania amazonensis and mouse macrophage cells was studied, as well as the enzyme inhibition against DNA topoisomerase II- The antileishmanial tests showed that the series-styryl 5'-6'-dimetoxifenetilamidas was the most cytotoxic, showing a higher selectivity for the macrophages. The series of styryl-benzyl and phenethyl-amide showed linear correlations between the logP values and % inhibition against L. amazonensis at a concentration of 50 M. It was observed that, in general, vehicles CD and PVP contributed to the bioavailability of amides regardless of the electronic effect of the substituent. The styryl-amides, for the most part, inhibited the enzymatic activity of topoisomerase II-.application/pdfporUniversidade Federal Rural do Rio de JaneiroPrograma de Pós-Graduação em QuímicaUFRRJBrasilInstituto de Ciências Exatasestiril-amidasatividade leishmanicidaDNA topoisomerase II-styryl-amidesantileishmania activityDNA-topoisomerase II-QuímicaSíntese e correlação entre a estrutura e a atividade leishmanicida de novas amidas estiril-substituídasinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisAKENDENGUE, B., NGOU-MILAMA, E., LAURENS, A., HOCQUEMILLER, R., Recent advances in the fight against leishmaniasis with natural products. Parasite, v. 6 n.1, p. 3–8, 1999. ANDERSEN, K. E.; LUNDT, B. F.; JORGENSEN, A. S.; BRAESTRUP,C. Oxadiazoles as bioisosteric transformations of carboxylic functionalities. 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| dc.title.por.fl_str_mv |
Síntese e correlação entre a estrutura e a atividade leishmanicida de novas amidas estiril-substituídas |
| title |
Síntese e correlação entre a estrutura e a atividade leishmanicida de novas amidas estiril-substituídas |
| spellingShingle |
Síntese e correlação entre a estrutura e a atividade leishmanicida de novas amidas estiril-substituídas Pissinate, Kenia estiril-amidas atividade leishmanicida DNA topoisomerase II- styryl-amides antileishmania activity DNA-topoisomerase II- Química |
| title_short |
Síntese e correlação entre a estrutura e a atividade leishmanicida de novas amidas estiril-substituídas |
| title_full |
Síntese e correlação entre a estrutura e a atividade leishmanicida de novas amidas estiril-substituídas |
| title_fullStr |
Síntese e correlação entre a estrutura e a atividade leishmanicida de novas amidas estiril-substituídas |
| title_full_unstemmed |
Síntese e correlação entre a estrutura e a atividade leishmanicida de novas amidas estiril-substituídas |
| title_sort |
Síntese e correlação entre a estrutura e a atividade leishmanicida de novas amidas estiril-substituídas |
| author |
Pissinate, Kenia |
| author_facet |
Pissinate, Kenia |
| author_role |
author |
| dc.contributor.author.fl_str_mv |
Pissinate, Kenia |
| dc.contributor.advisor1.fl_str_mv |
Lima, Aurea Echevarria Aznar Neves |
| dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/1879077396134052 |
| dc.contributor.advisor-co1.fl_str_mv |
Lima, Marco Edilson Freire de |
| dc.contributor.referee1.fl_str_mv |
Maciel, Maria Aparecida M. |
| dc.contributor.referee2.fl_str_mv |
Lima, Débora Decote Ricardo de |
| dc.contributor.referee3.fl_str_mv |
Oliveira, Mácia Cristina de |
| dc.contributor.referee4.fl_str_mv |
Lima, Célio Freire de |
| dc.contributor.referee5.fl_str_mv |
Castro, Rosane Nora |
| dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/8512959642500378 |
| contributor_str_mv |
Lima, Aurea Echevarria Aznar Neves Lima, Marco Edilson Freire de Maciel, Maria Aparecida M. Lima, Débora Decote Ricardo de Oliveira, Mácia Cristina de Lima, Célio Freire de Castro, Rosane Nora |
| dc.subject.por.fl_str_mv |
estiril-amidas atividade leishmanicida DNA topoisomerase II- |
| topic |
estiril-amidas atividade leishmanicida DNA topoisomerase II- styryl-amides antileishmania activity DNA-topoisomerase II- Química |
| dc.subject.eng.fl_str_mv |
styryl-amides antileishmania activity DNA-topoisomerase II- |
| dc.subject.cnpq.fl_str_mv |
Química |
| description |
Este trabalho relata a preparação de 25 estiril-amidas das quais 8 são inéditas, obtidas através da reação de substituição nucleofílica, via formação do cloreto de ácido, dos ácidos estiril-substituídos com os nucleófilos benzilamina, fenetilamina, 3,4-dimetoxifenetilamina, 3,4-metilenodioxifenetilamina em bons rendimentos. Também foram obtidos derivados N-estiril-N,N’-diciclo-hexil-uréias, via reação de acoplamento com a DCC. Além disso, foram preparados 5 compostos derivados da piperina, amida alcaloidal majoritária de Piper nigrum, sendo 4 deles inéditos na literatura. As técnicas espectroscópicas de IV e RMN de 1H e 13C foram utilizadas para caracterizar os produtos obtidos. Averiguou-se a biodisponibilidade em meio aquoso para os ensaios in vitro das estiril-amidas substituídas em três tipos de veículos (SME, PVP e -CD). Foi realizado, também o estudo da atividade citotóxica das estiril-amidas substituídas frente à forma promastigota de Leishmania amazonensis e às células de macrófagos de camundongo, além da inibição enzimática frente a DNA topoisomerase II- Os ensaios leishmanicidas mostraram que a série estiril-5’-6’-dimetoxifenetilamidas foi a mais citotóxica, apresentando uma maior seletividade diante dos macrófagos. As séries das estiril-benzil e fenetil-amidas apresentaram correlações lineares entre os valores de logP e os % de inibição frente a L. amazonensis na concentração de 50M. Pôde-se observar que, de maneira geral, os veículos CD e PVP contribuíram para a biodisponibilização das amidas independentemente do efeito eletrônico do substituinte. As estiril-amidas, em sua grande maioria, inibiram a atividade enzimática da topoisomerase II-. |
| publishDate |
2010 |
| dc.date.issued.fl_str_mv |
2010-08-27 |
| dc.date.accessioned.fl_str_mv |
2023-12-21T18:59:00Z |
| dc.date.available.fl_str_mv |
2023-12-21T18:59:00Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
| format |
doctoralThesis |
| status_str |
publishedVersion |
| dc.identifier.citation.fl_str_mv |
Pissinate, Kenia. Síntese e correlação entre a estrutura e a atividade leishmanicida de novas amidas estiril-substituídas. 2010. 160 f. Tese (Programa de Pós-Graduação em Química) - Universidade Federal Rural do Rio de Janeiro, Seropédica. |
| dc.identifier.uri.fl_str_mv |
https://rima.ufrrj.br/jspui/handle/20.500.14407/10204 |
| identifier_str_mv |
Pissinate, Kenia. Síntese e correlação entre a estrutura e a atividade leishmanicida de novas amidas estiril-substituídas. 2010. 160 f. Tese (Programa de Pós-Graduação em Química) - Universidade Federal Rural do Rio de Janeiro, Seropédica. |
| url |
https://rima.ufrrj.br/jspui/handle/20.500.14407/10204 |
| dc.language.iso.fl_str_mv |
por |
| language |
por |
| dc.relation.references.por.fl_str_mv |
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Fluid Phase Equilibria, v. 238, n. 2, p.186-192, 2005. |
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openAccess |
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Universidade Federal Rural do Rio de Janeiro |
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Programa de Pós-Graduação em Química |
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