Derivados dos ácidos clorogênico, cafeico e cinâmico: obtenção, avaliação da atividade antimicrobiana e de inibição enzimática
Autor(a) principal: | |
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Data de Publicação: | 2012 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Manancial - Repositório Digital da UFSM |
Texto Completo: | http://repositorio.ufsm.br/handle/1/8966 |
Resumo: | In recent years there has been an increase in researches for new enzyme inhibitors on medicinal plants used in the treatment of disorders such as schizophrenia, anxiety, amnesia, different stages of depression and bipolar affective disorder. The study of enzymatic inhibitors of prolyl oligopepetidase (POP) and acetylcholinesterase (AChE) are directly related to the treatment of central nervous sistem diseases. In a research with the species Hypericum brasiliense, native from Brazil, it was isolated as main secondary metabolite the chlorogenic acid, a compound able to inhibit POP and AChE. From this observation, three series of chlorogenic, caffeic and cinnamic acids derivatives were obtained through simple derivatization reactions and coupling with the amino acid proline. The derivatives were obtained by usual acetylation, methylation and esterification reactions with satisfactory yields of 50-90%. The couplings with the proline methyl ester were performed using either O-(7- azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU)/ diisopropylethylamine (DIEA) in dimethylformamide or isobutyl chloroformate/ Nmethylmorpholine in tetrahydrofuran. The derivatives were tested against the enzymes POP, AChE and dipeptidyl oligopeptidase (DPP IV). Also, a study was conducted to determine the antibacterial and antifungal activities of all derivatives. The capacity of the tested compounds to inhibit DPP IV and AChE was not exceptional. In contrast, the derivatives methyl ester and 1,7-acetonide obtained from chlorogenic acid, and caffeic acid and its methyl ester derivative showed selectivity and satisfactory performance as POP inhibitors, with IC50 values of 3 to 14 μM. All compounds showed moderate antimicrobial activity. |
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2017-02-102017-02-102012-04-27ADOLPHO, Luciana de Oliveira. CHLOROGENIC, CAFEIC AND CINNAMIC ACIDS DERIVATIVES: OBTENTION, ANTIMICROBIAL ACTIVITY AND ENZYMATIC INHIBITION EVALUATION. 2012. 145 f. Dissertação (Mestrado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2012.http://repositorio.ufsm.br/handle/1/8966In recent years there has been an increase in researches for new enzyme inhibitors on medicinal plants used in the treatment of disorders such as schizophrenia, anxiety, amnesia, different stages of depression and bipolar affective disorder. The study of enzymatic inhibitors of prolyl oligopepetidase (POP) and acetylcholinesterase (AChE) are directly related to the treatment of central nervous sistem diseases. In a research with the species Hypericum brasiliense, native from Brazil, it was isolated as main secondary metabolite the chlorogenic acid, a compound able to inhibit POP and AChE. From this observation, three series of chlorogenic, caffeic and cinnamic acids derivatives were obtained through simple derivatization reactions and coupling with the amino acid proline. The derivatives were obtained by usual acetylation, methylation and esterification reactions with satisfactory yields of 50-90%. The couplings with the proline methyl ester were performed using either O-(7- azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU)/ diisopropylethylamine (DIEA) in dimethylformamide or isobutyl chloroformate/ Nmethylmorpholine in tetrahydrofuran. The derivatives were tested against the enzymes POP, AChE and dipeptidyl oligopeptidase (DPP IV). Also, a study was conducted to determine the antibacterial and antifungal activities of all derivatives. The capacity of the tested compounds to inhibit DPP IV and AChE was not exceptional. In contrast, the derivatives methyl ester and 1,7-acetonide obtained from chlorogenic acid, and caffeic acid and its methyl ester derivative showed selectivity and satisfactory performance as POP inhibitors, with IC50 values of 3 to 14 μM. All compounds showed moderate antimicrobial activity.Nos últimos anos observa-se uma intensificação nas pesquisas por novos inibidores enzimáticos produzidos por plantas medicinais usadas no tratamento de transtornos mentais, tais como esquizofrenia, ansiedade, amnésia, diferentes estágios de depressão e o transtorno afetivo bipolar. O estudo de inibidores das enzimas prolil oligopepetidase (POP) e acetilcolinesterase (AChE), estão diretamente relacionados ao tratamento de tais enfermidades do sistema nervoso central (SNC). Em um trabalho com a planta medicinal Hypericum brasiliense, nativa do Brasil, foi isolado como um dos principais metabólitos secundários o ácido clorogênico, que demonstrou ter capacidade de inibir a POP e a AChE. A partir desta observação, foram obtidas três séries de derivados do ácido clorogênico, do ácido cafeico e do ácido cinâmico através de técnicas simples de derivatização e acoplamento com a prolina metil éster. Os derivados foram obtidos através de técnicas usuais de acetilação, metilação e esterificação, com rendimentos satisfatórios de 50-90 %. Já os acoplamentos com a prolina metil éster foram realizados com hexafluorofosfato de O-(7-azabenzotriazol-1-il)-N,N,N',N'- tetrametiluronio (HATU)/ diisopropiletilamina (DIEA) em dimetilformamida ou cloroformato de isobutila/ N-metilmorfolina em tetraidrofurano. Estes compostos foram avaliados quanto à capacidade inibitória das enzimas POP e AChE, bem como foram testados frente a enzima dipeptidil peptidade IV (DPP IV). Também foi realizado um estudo da atividade antimicrobiana dos derivados obtidos. Os resultados obtidos indicaram que, frente à DPP IV e AChE, os compostos avaliados não demonstraram significativa capacidade inibitória. Entretanto, o derivado metil éster e 1,7-acetonídeo obtidos a partir do ácido clorogênico, o cafeoato de metila e o próprio ácido cafeico mostraram capacidade inibitória seletiva para a POP, com valores de IC50 entre 3 e 14 μM. Com relação à atividade antimicrobiana, os derivados apresentaram moderada ação bactericida, destacando-se os compostos derivados do ácido cinâmico por serem fungicidas.Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorapplication/pdfporUniversidade Federal de Santa MariaPrograma de Pós-Graduação em FarmacologiaUFSMBRFarmacologiaCafeoilCinamoilProlil oligopeptidaseDipeptidil peptidase IVAcetilcolinesteraseCafeoylCinnamoylProlyl oligopeptidaseDipeptidil peptidaseAcetylcholinesteraseCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIADerivados dos ácidos clorogênico, cafeico e cinâmico: obtenção, avaliação da atividade antimicrobiana e de inibição enzimáticaChlorogenic, cafeic and cinnamic acids derivatives: obtention, antimicrobial activity and enzymatic inhibition evaluationinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisDalcol, Ionara Irionhttp://lattes.cnpq.br/9769548819312192Maldaner, Gracielahttp://lattes.cnpq.br/6500796131690728Baldisserotto, Bernardohttp://lattes.cnpq.br/1036046601275319http://lattes.cnpq.br/5487129225788491Adolpho, Luciana de Oliveira201000000000400300300500500b247746a-8793-4e70-954f-639310a0e179967220b2-88c5-4469-ad36-691ea33e3098b0db7504-a42c-44d0-b7f0-992c14108c1aa64e0440-e917-4c31-ad62-51b4ea8f37fdinfo:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALADOLFHO, LUCIANA DE OLIVEIRA.pdfapplication/pdf2346479http://repositorio.ufsm.br/bitstream/1/8966/1/ADOLFHO%2c%20LUCIANA%20DE%20OLIVEIRA.pdf564d2fa0d2803f52abd9aaf39e899b2aMD51TEXTADOLFHO, LUCIANA DE OLIVEIRA.pdf.txtADOLFHO, LUCIANA DE OLIVEIRA.pdf.txtExtracted texttext/plain174017http://repositorio.ufsm.br/bitstream/1/8966/2/ADOLFHO%2c%20LUCIANA%20DE%20OLIVEIRA.pdf.txtc0bec01e1c282d31471ed141bc37dcb6MD52THUMBNAILADOLFHO, LUCIANA DE OLIVEIRA.pdf.jpgADOLFHO, LUCIANA DE OLIVEIRA.pdf.jpgIM Thumbnailimage/jpeg4966http://repositorio.ufsm.br/bitstream/1/8966/3/ADOLFHO%2c%20LUCIANA%20DE%20OLIVEIRA.pdf.jpgaa3cf88c3322d19bf459e66576c7f3e6MD531/89662022-06-27 12:56:06.831oai:repositorio.ufsm.br:1/8966Repositório Institucionalhttp://repositorio.ufsm.br/PUBhttp://repositorio.ufsm.br/oai/requestopendoar:39132022-06-27T15:56:06Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
Derivados dos ácidos clorogênico, cafeico e cinâmico: obtenção, avaliação da atividade antimicrobiana e de inibição enzimática |
dc.title.alternative.eng.fl_str_mv |
Chlorogenic, cafeic and cinnamic acids derivatives: obtention, antimicrobial activity and enzymatic inhibition evaluation |
title |
Derivados dos ácidos clorogênico, cafeico e cinâmico: obtenção, avaliação da atividade antimicrobiana e de inibição enzimática |
spellingShingle |
Derivados dos ácidos clorogênico, cafeico e cinâmico: obtenção, avaliação da atividade antimicrobiana e de inibição enzimática Adolpho, Luciana de Oliveira Cafeoil Cinamoil Prolil oligopeptidase Dipeptidil peptidase IV Acetilcolinesterase Cafeoyl Cinnamoyl Prolyl oligopeptidase Dipeptidil peptidase Acetylcholinesterase CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
title_short |
Derivados dos ácidos clorogênico, cafeico e cinâmico: obtenção, avaliação da atividade antimicrobiana e de inibição enzimática |
title_full |
Derivados dos ácidos clorogênico, cafeico e cinâmico: obtenção, avaliação da atividade antimicrobiana e de inibição enzimática |
title_fullStr |
Derivados dos ácidos clorogênico, cafeico e cinâmico: obtenção, avaliação da atividade antimicrobiana e de inibição enzimática |
title_full_unstemmed |
Derivados dos ácidos clorogênico, cafeico e cinâmico: obtenção, avaliação da atividade antimicrobiana e de inibição enzimática |
title_sort |
Derivados dos ácidos clorogênico, cafeico e cinâmico: obtenção, avaliação da atividade antimicrobiana e de inibição enzimática |
author |
Adolpho, Luciana de Oliveira |
author_facet |
Adolpho, Luciana de Oliveira |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Dalcol, Ionara Irion |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/9769548819312192 |
dc.contributor.referee1.fl_str_mv |
Maldaner, Graciela |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/6500796131690728 |
dc.contributor.referee2.fl_str_mv |
Baldisserotto, Bernardo |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/1036046601275319 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/5487129225788491 |
dc.contributor.author.fl_str_mv |
Adolpho, Luciana de Oliveira |
contributor_str_mv |
Dalcol, Ionara Irion Maldaner, Graciela Baldisserotto, Bernardo |
dc.subject.por.fl_str_mv |
Cafeoil Cinamoil Prolil oligopeptidase Dipeptidil peptidase IV Acetilcolinesterase |
topic |
Cafeoil Cinamoil Prolil oligopeptidase Dipeptidil peptidase IV Acetilcolinesterase Cafeoyl Cinnamoyl Prolyl oligopeptidase Dipeptidil peptidase Acetylcholinesterase CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
dc.subject.eng.fl_str_mv |
Cafeoyl Cinnamoyl Prolyl oligopeptidase Dipeptidil peptidase Acetylcholinesterase |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA |
description |
In recent years there has been an increase in researches for new enzyme inhibitors on medicinal plants used in the treatment of disorders such as schizophrenia, anxiety, amnesia, different stages of depression and bipolar affective disorder. The study of enzymatic inhibitors of prolyl oligopepetidase (POP) and acetylcholinesterase (AChE) are directly related to the treatment of central nervous sistem diseases. In a research with the species Hypericum brasiliense, native from Brazil, it was isolated as main secondary metabolite the chlorogenic acid, a compound able to inhibit POP and AChE. From this observation, three series of chlorogenic, caffeic and cinnamic acids derivatives were obtained through simple derivatization reactions and coupling with the amino acid proline. The derivatives were obtained by usual acetylation, methylation and esterification reactions with satisfactory yields of 50-90%. The couplings with the proline methyl ester were performed using either O-(7- azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU)/ diisopropylethylamine (DIEA) in dimethylformamide or isobutyl chloroformate/ Nmethylmorpholine in tetrahydrofuran. The derivatives were tested against the enzymes POP, AChE and dipeptidyl oligopeptidase (DPP IV). Also, a study was conducted to determine the antibacterial and antifungal activities of all derivatives. The capacity of the tested compounds to inhibit DPP IV and AChE was not exceptional. In contrast, the derivatives methyl ester and 1,7-acetonide obtained from chlorogenic acid, and caffeic acid and its methyl ester derivative showed selectivity and satisfactory performance as POP inhibitors, with IC50 values of 3 to 14 μM. All compounds showed moderate antimicrobial activity. |
publishDate |
2012 |
dc.date.issued.fl_str_mv |
2012-04-27 |
dc.date.accessioned.fl_str_mv |
2017-02-10 |
dc.date.available.fl_str_mv |
2017-02-10 |
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 |
ADOLPHO, Luciana de Oliveira. CHLOROGENIC, CAFEIC AND CINNAMIC ACIDS DERIVATIVES: OBTENTION, ANTIMICROBIAL ACTIVITY AND ENZYMATIC INHIBITION EVALUATION. 2012. 145 f. Dissertação (Mestrado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2012. |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/8966 |
identifier_str_mv |
ADOLPHO, Luciana de Oliveira. CHLOROGENIC, CAFEIC AND CINNAMIC ACIDS DERIVATIVES: OBTENTION, ANTIMICROBIAL ACTIVITY AND ENZYMATIC INHIBITION EVALUATION. 2012. 145 f. Dissertação (Mestrado em Farmácia) - Universidade Federal de Santa Maria, Santa Maria, 2012. |
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http://repositorio.ufsm.br/handle/1/8966 |
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