Atividade antinociceptiva e antioxidante do derivado tiofênico 2-amino-4,5,6,7-tetrahidro-benzotiofeno-3-carbonitrila (6CN) em camundongos
Autor(a) principal: | |
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Data de Publicação: | 2014 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Biblioteca Digital de Teses e Dissertações da UFPB |
Texto Completo: | https://repositorio.ufpb.br/jspui/handle/tede/6806 |
Resumo: | Of heterocyclic compounds, thiophenols stand out due to their potential as a prototype for the development of new drugs, are known to exhibit various biological activities. The thiophenic derivative 2-amino-4 ,5,6,7-tetrahydro-benzothiophene-3-carbonitrile (6CN) is synthesized by reacting Gewald. This study aimed to investigate the antinociceptive and antioxidant activity of the thiophenic derivative 2 - amino - 4,5,6,7 - tetrahydro - benzothiophene - 3 - carbonitrile (6CN) in Swiss mice. Initially, the LD50 (lethal dose 50 %) of 6CN, the result was 557.5 mg/kg. All different doses tested in pharmacological screening tests, induced to psicodepressant behavioral changes such as reduced ambulation and decreased response to touch and analgesia. Then tests were performed to evaluate the muscle relaxant, sedative and anxiolytic activity. The 6CN presented relaxant and sedative activity at doses of 50 and 100 mg/kg in the rotarod and the thiopental sleep induction test, respectively, and anxiolytic activity at doses of 25 and 50 mg/kg in the test plus maze. The antinociceptive activity was tested using the writhing induced by acetic acid, formalin and hot plate tests. The 6CN increased the latency to the onset of writhing induced by acetic acid and reduced the number of writhes when compared to the control group at doses of 25, 50 and 100 mg/kg. In the formalin test, 6CN 100 mg/kg dose reduced the time of paw licking in the neurogenic phase (0-5 min). The licking time reduced at all doses tested during the subsequent inflammatory phase (15-30 min). In the hot plate test, 6CN increased the latency time at doses of 50 and 100 mg/kg in the first 30 min. Using 6CN 100 mg/kg dose the effect lasted during all the experiment. The study used the opioid, adenosinergic, dopaminergic, muscarinic, L-arginine-nitric oxide, GABAergic and sensitive K + channels to ATP (K+ATP) pathways as pharmacological tools to elucidate the antinociceptive action of 6CN. Caffein reversed the antinociception produced by 6CN in the neurogenic and inflammatory phase of the formalin test. Whereas haloperidol reversed only the second phase of the formalin test, suggesting the involvement of adenosine and dopamine receptors. The 6CN showed antioxidant activity, evaluated by testing the scavenging activity of DPPH and trolox equivalent antioxidant capacity (CAET), with EC50 values of 4.7 and 1.1 g/ml, respectively. Therefore, this study demonstrated that the 6CN has anxiolytic, antinociceptive activity , with participation of adenosinergic and dopaminergic systems. It also has antioxidant activity for DPPH and ABTS radicals. |
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Atividade antinociceptiva e antioxidante do derivado tiofênico 2-amino-4,5,6,7-tetrahidro-benzotiofeno-3-carbonitrila (6CN) em camundongosAntinociceptive and antioxidant activity of the thiophenic derivative 2,3-dimethyl-4,5,6,7-tetrahydrobenzothiophene (6CN).Atividade antinociceptivaAtividade antioxidanteCompostos heterocíclicosAntinociceptive activityAntioxidant activityHeterocyclic compoundsCIENCIAS BIOLOGICAS::FARMACOLOGIAOf heterocyclic compounds, thiophenols stand out due to their potential as a prototype for the development of new drugs, are known to exhibit various biological activities. The thiophenic derivative 2-amino-4 ,5,6,7-tetrahydro-benzothiophene-3-carbonitrile (6CN) is synthesized by reacting Gewald. This study aimed to investigate the antinociceptive and antioxidant activity of the thiophenic derivative 2 - amino - 4,5,6,7 - tetrahydro - benzothiophene - 3 - carbonitrile (6CN) in Swiss mice. Initially, the LD50 (lethal dose 50 %) of 6CN, the result was 557.5 mg/kg. All different doses tested in pharmacological screening tests, induced to psicodepressant behavioral changes such as reduced ambulation and decreased response to touch and analgesia. Then tests were performed to evaluate the muscle relaxant, sedative and anxiolytic activity. The 6CN presented relaxant and sedative activity at doses of 50 and 100 mg/kg in the rotarod and the thiopental sleep induction test, respectively, and anxiolytic activity at doses of 25 and 50 mg/kg in the test plus maze. The antinociceptive activity was tested using the writhing induced by acetic acid, formalin and hot plate tests. The 6CN increased the latency to the onset of writhing induced by acetic acid and reduced the number of writhes when compared to the control group at doses of 25, 50 and 100 mg/kg. In the formalin test, 6CN 100 mg/kg dose reduced the time of paw licking in the neurogenic phase (0-5 min). The licking time reduced at all doses tested during the subsequent inflammatory phase (15-30 min). In the hot plate test, 6CN increased the latency time at doses of 50 and 100 mg/kg in the first 30 min. Using 6CN 100 mg/kg dose the effect lasted during all the experiment. The study used the opioid, adenosinergic, dopaminergic, muscarinic, L-arginine-nitric oxide, GABAergic and sensitive K + channels to ATP (K+ATP) pathways as pharmacological tools to elucidate the antinociceptive action of 6CN. Caffein reversed the antinociception produced by 6CN in the neurogenic and inflammatory phase of the formalin test. Whereas haloperidol reversed only the second phase of the formalin test, suggesting the involvement of adenosine and dopamine receptors. The 6CN showed antioxidant activity, evaluated by testing the scavenging activity of DPPH and trolox equivalent antioxidant capacity (CAET), with EC50 values of 4.7 and 1.1 g/ml, respectively. Therefore, this study demonstrated that the 6CN has anxiolytic, antinociceptive activity , with participation of adenosinergic and dopaminergic systems. It also has antioxidant activity for DPPH and ABTS radicals.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESDos compostos heterocíclicos, destacam-se os tiofenóis devido à sua potencialidade como protótipo para o desenvolvimento de novos fármacos, são conhecidos por apresentar várias atividades biológicas. O derivado tiofênico 2-amino-4,5,6,7-tetrahidro-benzotiofeno-3-carbonitrila (6CN) é sintetizado através da reação de Gewald. O trabalho teve como objetivo investigar a atividade antinociceptiva e antioxidante do 6CN em camundongos. Inicialmente, foi realizada a pesquisa da dose letal 50% (DL50) do 6CN, cujo resultado foi de 557,5 mg/kg. Na triagem farmacológica comportamental, as diferentes doses testadas do 6CN induziram alterações comportamentais psicodepressoras, como redução da ambulação e resposta ao toque diminuída e analgesia. Foram avaliadas as atividades miorrelaxante, sedativa e ansiolítica. O 6CN apresentou atividade miorrelaxante e sedativa nas doses de 50 e 100 mg/kg nos testes do rota rod e indução do sono pelo tiopental, respectivamente, e atividade ansiolítica nas doses de 25 e 50 mg/kg no teste do labirinto em cruz elevado. Para avaliar a atividade antinociceptiva foram utilizados os testes das contorções abdominais induzidas por ácido acético, da formalina e da placa quente. O 6CN aumentou a latência para o inicio das contorções abdominais induzidas por ácido acético e reduziu o número de contorções, quando comparado ao grupo controle, nas doses de 25, 50 e 100 mg/kg. No teste da formalina, a dose de 100 mg/kg diminuiu o tempo de lambida da pata na fase neurogênica (0-5 min), enquanto na fase inflamatória (15-30 min) houve diminuição no tempo de lambida da pata em todas as doses testadas. No teste da placa quente, o 6CN aumentou a latência nas doses de 50 e 100 mg/kg nos primeiros 30 mim e a dose de 100 mg/kg manteve o efeito nos tempos de 60 e 120 min. Com o objetivo de elucidar o mecanismo de ação envolvido no efeito antinociceptivo do 6CN foram testadas as seguintes vias: opioide, adenosinérgica, dopaminérgica, muscarínica, L-arginina-óxido nítrico, gabaérgica e a via dos canais de K+ sensíveis ao ATP (K+ATP) no teste da formalina. A antinocicepção produzida pelo 6CN foi revertida pela cafeína na fase neurogênica e inflamatória e pelo haloperidol na segunda fase do teste da formalina, sugerindo o envolvimento dos receptores da adenosina e dopamina. O 6CN apresentou atividade antioxidante, avaliada pelos testes da atividade sequestradora do DPPH e capacidade antioxidante equivalente ao trolox (CAET), com valores de CE50 de 4,7 e 1,1 μg/ml, respectivamente. Este trabalho demonstrou que o 6CN possui atividade antinociceptiva com participação dos sistemas adenosinérgico e dopaminérgico. Além disso, possui atividade antioxidante para os radicais DPPH e ABTS.Universidade Federal da ParaíbaBRFarmacologiaPrograma de Pós-Graduação em Produtos Naturais e Sintéticos BioativosUFPBAlmeida, Reinaldo Nobrega dehttp://lattes.cnpq.br/5034028656386134Assis, Temilce Simões dehttp://lattes.cnpq.br/2505767977557671Penha, Antônia Rosângela Soares2015-05-14T12:59:58Z2018-07-21T00:25:06Z2014-09-112018-07-21T00:25:06Z2014-02-21info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfPENHA, Antônia Rosângela Soares. Atividade antinociceptiva e antioxidante do derivado tiofênico 2-amino-4,5,6,7-tetrahidro-benzotiofeno-3-carbonitrila (6CN) em camundongos. 2014. 114 f. Tese (Doutorado em Produtos Naturais e Sintéticos Bioativos) - Universidade Federal da Paraíba, João Pessoa, 2014.https://repositorio.ufpb.br/jspui/handle/tede/6806porinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFPBinstname:Universidade Federal da Paraíba (UFPB)instacron:UFPB2018-09-06T01:57:19Zoai:repositorio.ufpb.br:tede/6806Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufpb.br/PUBhttp://tede.biblioteca.ufpb.br:8080/oai/requestdiretoria@ufpb.br|| diretoria@ufpb.bropendoar:2018-09-06T01:57:19Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB)false |
dc.title.none.fl_str_mv |
Atividade antinociceptiva e antioxidante do derivado tiofênico 2-amino-4,5,6,7-tetrahidro-benzotiofeno-3-carbonitrila (6CN) em camundongos Antinociceptive and antioxidant activity of the thiophenic derivative 2,3-dimethyl-4,5,6,7-tetrahydrobenzothiophene (6CN). |
title |
Atividade antinociceptiva e antioxidante do derivado tiofênico 2-amino-4,5,6,7-tetrahidro-benzotiofeno-3-carbonitrila (6CN) em camundongos |
spellingShingle |
Atividade antinociceptiva e antioxidante do derivado tiofênico 2-amino-4,5,6,7-tetrahidro-benzotiofeno-3-carbonitrila (6CN) em camundongos Penha, Antônia Rosângela Soares Atividade antinociceptiva Atividade antioxidante Compostos heterocíclicos Antinociceptive activity Antioxidant activity Heterocyclic compounds CIENCIAS BIOLOGICAS::FARMACOLOGIA |
title_short |
Atividade antinociceptiva e antioxidante do derivado tiofênico 2-amino-4,5,6,7-tetrahidro-benzotiofeno-3-carbonitrila (6CN) em camundongos |
title_full |
Atividade antinociceptiva e antioxidante do derivado tiofênico 2-amino-4,5,6,7-tetrahidro-benzotiofeno-3-carbonitrila (6CN) em camundongos |
title_fullStr |
Atividade antinociceptiva e antioxidante do derivado tiofênico 2-amino-4,5,6,7-tetrahidro-benzotiofeno-3-carbonitrila (6CN) em camundongos |
title_full_unstemmed |
Atividade antinociceptiva e antioxidante do derivado tiofênico 2-amino-4,5,6,7-tetrahidro-benzotiofeno-3-carbonitrila (6CN) em camundongos |
title_sort |
Atividade antinociceptiva e antioxidante do derivado tiofênico 2-amino-4,5,6,7-tetrahidro-benzotiofeno-3-carbonitrila (6CN) em camundongos |
author |
Penha, Antônia Rosângela Soares |
author_facet |
Penha, Antônia Rosângela Soares |
author_role |
author |
dc.contributor.none.fl_str_mv |
Almeida, Reinaldo Nobrega de http://lattes.cnpq.br/5034028656386134 Assis, Temilce Simões de http://lattes.cnpq.br/2505767977557671 |
dc.contributor.author.fl_str_mv |
Penha, Antônia Rosângela Soares |
dc.subject.por.fl_str_mv |
Atividade antinociceptiva Atividade antioxidante Compostos heterocíclicos Antinociceptive activity Antioxidant activity Heterocyclic compounds CIENCIAS BIOLOGICAS::FARMACOLOGIA |
topic |
Atividade antinociceptiva Atividade antioxidante Compostos heterocíclicos Antinociceptive activity Antioxidant activity Heterocyclic compounds CIENCIAS BIOLOGICAS::FARMACOLOGIA |
description |
Of heterocyclic compounds, thiophenols stand out due to their potential as a prototype for the development of new drugs, are known to exhibit various biological activities. The thiophenic derivative 2-amino-4 ,5,6,7-tetrahydro-benzothiophene-3-carbonitrile (6CN) is synthesized by reacting Gewald. This study aimed to investigate the antinociceptive and antioxidant activity of the thiophenic derivative 2 - amino - 4,5,6,7 - tetrahydro - benzothiophene - 3 - carbonitrile (6CN) in Swiss mice. Initially, the LD50 (lethal dose 50 %) of 6CN, the result was 557.5 mg/kg. All different doses tested in pharmacological screening tests, induced to psicodepressant behavioral changes such as reduced ambulation and decreased response to touch and analgesia. Then tests were performed to evaluate the muscle relaxant, sedative and anxiolytic activity. The 6CN presented relaxant and sedative activity at doses of 50 and 100 mg/kg in the rotarod and the thiopental sleep induction test, respectively, and anxiolytic activity at doses of 25 and 50 mg/kg in the test plus maze. The antinociceptive activity was tested using the writhing induced by acetic acid, formalin and hot plate tests. The 6CN increased the latency to the onset of writhing induced by acetic acid and reduced the number of writhes when compared to the control group at doses of 25, 50 and 100 mg/kg. In the formalin test, 6CN 100 mg/kg dose reduced the time of paw licking in the neurogenic phase (0-5 min). The licking time reduced at all doses tested during the subsequent inflammatory phase (15-30 min). In the hot plate test, 6CN increased the latency time at doses of 50 and 100 mg/kg in the first 30 min. Using 6CN 100 mg/kg dose the effect lasted during all the experiment. The study used the opioid, adenosinergic, dopaminergic, muscarinic, L-arginine-nitric oxide, GABAergic and sensitive K + channels to ATP (K+ATP) pathways as pharmacological tools to elucidate the antinociceptive action of 6CN. Caffein reversed the antinociception produced by 6CN in the neurogenic and inflammatory phase of the formalin test. Whereas haloperidol reversed only the second phase of the formalin test, suggesting the involvement of adenosine and dopamine receptors. The 6CN showed antioxidant activity, evaluated by testing the scavenging activity of DPPH and trolox equivalent antioxidant capacity (CAET), with EC50 values of 4.7 and 1.1 g/ml, respectively. Therefore, this study demonstrated that the 6CN has anxiolytic, antinociceptive activity , with participation of adenosinergic and dopaminergic systems. It also has antioxidant activity for DPPH and ABTS radicals. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014-09-11 2014-02-21 2015-05-14T12:59:58Z 2018-07-21T00:25:06Z 2018-07-21T00:25:06Z |
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.uri.fl_str_mv |
PENHA, Antônia Rosângela Soares. Atividade antinociceptiva e antioxidante do derivado tiofênico 2-amino-4,5,6,7-tetrahidro-benzotiofeno-3-carbonitrila (6CN) em camundongos. 2014. 114 f. Tese (Doutorado em Produtos Naturais e Sintéticos Bioativos) - Universidade Federal da Paraíba, João Pessoa, 2014. https://repositorio.ufpb.br/jspui/handle/tede/6806 |
identifier_str_mv |
PENHA, Antônia Rosângela Soares. Atividade antinociceptiva e antioxidante do derivado tiofênico 2-amino-4,5,6,7-tetrahidro-benzotiofeno-3-carbonitrila (6CN) em camundongos. 2014. 114 f. Tese (Doutorado em Produtos Naturais e Sintéticos Bioativos) - Universidade Federal da Paraíba, João Pessoa, 2014. |
url |
https://repositorio.ufpb.br/jspui/handle/tede/6806 |
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por |
language |
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info:eu-repo/semantics/openAccess |
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openAccess |
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dc.publisher.none.fl_str_mv |
Universidade Federal da Paraíba BR Farmacologia Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos UFPB |
publisher.none.fl_str_mv |
Universidade Federal da Paraíba BR Farmacologia Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos UFPB |
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reponame:Biblioteca Digital de Teses e Dissertações da UFPB instname:Universidade Federal da Paraíba (UFPB) instacron:UFPB |
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Universidade Federal da Paraíba (UFPB) |
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UFPB |
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UFPB |
reponame_str |
Biblioteca Digital de Teses e Dissertações da UFPB |
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Biblioteca Digital de Teses e Dissertações da UFPB |
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Biblioteca Digital de Teses e Dissertações da UFPB - Universidade Federal da Paraíba (UFPB) |
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diretoria@ufpb.br|| diretoria@ufpb.br |
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