Estudo químico de Bowdichia virgilioides (Fabaceae) na busca de inibidores seletivos de cisteíno peptidases

Detalhes bibliográficos
Autor(a) principal: Silva, Taynara Lopes
Data de Publicação: 2014
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFSCAR
Texto Completo: https://repositorio.ufscar.br/handle/ufscar/7670
Resumo: This work describes the isolation of bioactive secondary metabolites of the plant species Bowdichia virgilioides in the search for selective inhibitors of cathepsins K, L and V. Cathepsins are enzymes that have as primary function the degradation of proteins in the lysosomes, and are also related to development of diseases such as osteoporosis, rheumatoid arthritis, atherosclerosis and various cancers. This dissertation describes the bioactivity-guided study of the ethanol extracts and fractions obtained from the stems and leaves of B. virgilioides through fluorimetric inhibition assay of the enzymes studied. The extracts of B. virgilioides were subjected to successive fractionations using different chromatographic techniques leading to several pure substances. The isolated substances had their structures elucidated by NMR uni- and bi-dimensional and mass spectrometry. The hexane and ethyl acetate fractions of stem afforded eleven substances: 2 triterpenes, lupeol and lupenona; the mixture of steroids β-sitosterol and stigmasterol; 1 ester derivative of trans pcoumaric acid; 1 furofuran lignan, syringaresinol; 1Benzofuran derivative, bowdenol; 1 coumestrol derivative, 8-methoxycoumestrol, and 3 isoflavones, 7,3'-dihydroxy-4'- methoxyisoflavone, 5,4'-dihydroxy-7'-methoxyisoflavone and 4-hydroxy-7-methoxyisoflavone. All compounds were tested on their ability to inhibit the enzymes at a concentration of 100μM. 8-Methoxycoumestrol showed inhibition superior to 70% for cathepsin V. The potency of this inhibitor was determined and the IC50 value was found to be 17.4 ± 1.0μM for cathepsin V. The ester derivative of trans p-coumaric acid also showed good inhibition above 70% for cathepsin L and V at a concentration of 50μg/mL. So, a series of 8 esters derived from p-hydroxybenzoic acid, p-coumaric acid, cinnamic and ferulic were prepared, and have been evaluated regarding their inhibitory activities of the cathepsins at a concentration of 100μM. n-Octyl pcoumarate ester showed the best percentage inhibition for the three enzymes. The constituents of the hexane fraction of leaves of B. virgilioides were analyzed using the techniques 1H NMR and GC-MS.
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spelling Silva, Taynara LopesVieira, Paulo Cezarhttp://lattes.cnpq.br/8923844563320377http://lattes.cnpq.br/9412487106628965e222ef86-105c-47f3-b5d1-e50a9702482f2016-10-04T18:49:43Z2016-10-04T18:49:43Z2014-03-31SILVA, Taynara Lopes. Estudo químico de Bowdichia virgilioides (Fabaceae) na busca de inibidores seletivos de cisteíno peptidases. 2014. Dissertação (Mestrado em Química) – Universidade Federal de São Carlos, São Carlos, 2014. Disponível em: https://repositorio.ufscar.br/handle/ufscar/7670.https://repositorio.ufscar.br/handle/ufscar/7670This work describes the isolation of bioactive secondary metabolites of the plant species Bowdichia virgilioides in the search for selective inhibitors of cathepsins K, L and V. Cathepsins are enzymes that have as primary function the degradation of proteins in the lysosomes, and are also related to development of diseases such as osteoporosis, rheumatoid arthritis, atherosclerosis and various cancers. This dissertation describes the bioactivity-guided study of the ethanol extracts and fractions obtained from the stems and leaves of B. virgilioides through fluorimetric inhibition assay of the enzymes studied. The extracts of B. virgilioides were subjected to successive fractionations using different chromatographic techniques leading to several pure substances. The isolated substances had their structures elucidated by NMR uni- and bi-dimensional and mass spectrometry. The hexane and ethyl acetate fractions of stem afforded eleven substances: 2 triterpenes, lupeol and lupenona; the mixture of steroids β-sitosterol and stigmasterol; 1 ester derivative of trans pcoumaric acid; 1 furofuran lignan, syringaresinol; 1Benzofuran derivative, bowdenol; 1 coumestrol derivative, 8-methoxycoumestrol, and 3 isoflavones, 7,3'-dihydroxy-4'- methoxyisoflavone, 5,4'-dihydroxy-7'-methoxyisoflavone and 4-hydroxy-7-methoxyisoflavone. All compounds were tested on their ability to inhibit the enzymes at a concentration of 100μM. 8-Methoxycoumestrol showed inhibition superior to 70% for cathepsin V. The potency of this inhibitor was determined and the IC50 value was found to be 17.4 ± 1.0μM for cathepsin V. The ester derivative of trans p-coumaric acid also showed good inhibition above 70% for cathepsin L and V at a concentration of 50μg/mL. So, a series of 8 esters derived from p-hydroxybenzoic acid, p-coumaric acid, cinnamic and ferulic were prepared, and have been evaluated regarding their inhibitory activities of the cathepsins at a concentration of 100μM. n-Octyl pcoumarate ester showed the best percentage inhibition for the three enzymes. The constituents of the hexane fraction of leaves of B. virgilioides were analyzed using the techniques 1H NMR and GC-MS.Este trabalho descreve o isolamento de metabólitos secundários bioativos da espécie vegetal Bowdichia virgilioides buscando inibidores seletivos das catepsinas K, L e V. As catepsinas são enzimas que têm como função primária a degradação de proteínas nos lisossomos e também estão relacionadas ao desenvolvimento de doenças como osteoporose, artrite reumatoide, aterosclerose e diferentes tipos de cânceres. Neste projeto foi realizado o estudo biomonitorado dos extratos etanólicos do caule e das folhas das respectivas frações obtidas de B. virgilioides por ensaio fluorimétrico de inibição frente às enzimas estudadas. Os extratos de B. virgilioides foram submetidos a sucessivos fracionamentos utilizando diferentes técnicas cromatográficas levando a várias substâncias puras. As substâncias isoladas tiveram suas estruturas elucidadas por RMN uni- e bi-dimensionais e espectrometria de massas. O estudo das frações hexânica e de acetato de etila do caule resultou no isolamento de onze substâncias sendo 2 triterpenos: lupeol e lupenona; a mistura dos esteroides β-sitosterol e estigmasterol; 1 éster derivado do ácido trans pcumárico; 1 lignana furofurânica: siringaresinol; 1 derivado benzofurano: bowdenol; 1 derivado do cumestrol: 8-metoxicumestrol e 3 isoflavonas: 7, 3’-diidroxi-4’metoxiisoflavona, 5, 4’-diidroxi-7’-metoxi-isoflavona e 4-hidroxi-7-metoxi-isoflavona. Todas foram ensaiadas na concentração de 100 μM. O 8-metoxicumestrol apresentou inibição superior a 70% para a catepsina V. A potência deste inibidor foi determinada e o valor de IC50 encontrado foi de 17,4 ± 1,0 μM frente à catepsina V. O éster derivado do ácido trans p-cumárico apresentou inibição superior a 70% para as catepsinas L e V na concentração de 50μg/mL. Então, foram preparados uma série de 8 ésteres derivados dos ácidos p-hidroxibenzóico, p-cumárico, cinâmico e ferúlico, que foram avaliados com relação às suas atividades inibitórias frente às catepsinas estudas na concentração de 100μM. O ester p-Cumarato de n-octila apresentou melhor porcentagem de inibição para as três enzimas. Os constituintes da fração hexânica das folhas de B. virgilioides foram analisados em mistura utilizando as técnicas de RMN 1H e CG-EM.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)porUniversidade Federal de São CarlosCâmpus São CarlosPrograma de Pós-Graduação em Química - PPGQUFSCarProdutos naturaisEnzimasInibidores enzimáticosCerradosCIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ORGANICA::FISICO-QUIMICA ORGANICAEstudo químico de Bowdichia virgilioides (Fabaceae) na busca de inibidores seletivos de cisteíno peptidasesChemical study of bowdichia virgilioides (Fabaceae) in the search for selective inhibitors of cysteine peptidasesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisOnline60074f71c3f-154a-42a0-9eaa-a32f1f60d4c4info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFSCARinstname:Universidade Federal de São Carlos (UFSCAR)instacron:UFSCARORIGINALDissTLS.pdfDissTLS.pdfapplication/pdf2364039https://repositorio.ufscar.br/bitstream/ufscar/7670/1/DissTLS.pdf1ad7c970d8a6bfb5f467365e9eac2564MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81957https://repositorio.ufscar.br/bitstream/ufscar/7670/2/license.txtae0398b6f8b235e40ad82cba6c50031dMD52TEXTDissTLS.pdf.txtDissTLS.pdf.txtExtracted texttext/plain144784https://repositorio.ufscar.br/bitstream/ufscar/7670/3/DissTLS.pdf.txtab5a6eb76ebb216fa195b18f1b8f0596MD53THUMBNAILDissTLS.pdf.jpgDissTLS.pdf.jpgIM Thumbnailimage/jpeg9455https://repositorio.ufscar.br/bitstream/ufscar/7670/4/DissTLS.pdf.jpgf07e333c1d2b55d1ca4e58b61feec155MD54ufscar/76702023-09-18 18:30:56.536oai:repositorio.ufscar.br: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Repositório InstitucionalPUBhttps://repositorio.ufscar.br/oai/requestopendoar:43222023-09-18T18:30:56Repositório Institucional da UFSCAR - Universidade Federal de São Carlos (UFSCAR)false
dc.title.por.fl_str_mv Estudo químico de Bowdichia virgilioides (Fabaceae) na busca de inibidores seletivos de cisteíno peptidases
dc.title.alternative.eng.fl_str_mv Chemical study of bowdichia virgilioides (Fabaceae) in the search for selective inhibitors of cysteine peptidases
title Estudo químico de Bowdichia virgilioides (Fabaceae) na busca de inibidores seletivos de cisteíno peptidases
spellingShingle Estudo químico de Bowdichia virgilioides (Fabaceae) na busca de inibidores seletivos de cisteíno peptidases
Silva, Taynara Lopes
Produtos naturais
Enzimas
Inibidores enzimáticos
Cerrados
CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ORGANICA::FISICO-QUIMICA ORGANICA
title_short Estudo químico de Bowdichia virgilioides (Fabaceae) na busca de inibidores seletivos de cisteíno peptidases
title_full Estudo químico de Bowdichia virgilioides (Fabaceae) na busca de inibidores seletivos de cisteíno peptidases
title_fullStr Estudo químico de Bowdichia virgilioides (Fabaceae) na busca de inibidores seletivos de cisteíno peptidases
title_full_unstemmed Estudo químico de Bowdichia virgilioides (Fabaceae) na busca de inibidores seletivos de cisteíno peptidases
title_sort Estudo químico de Bowdichia virgilioides (Fabaceae) na busca de inibidores seletivos de cisteíno peptidases
author Silva, Taynara Lopes
author_facet Silva, Taynara Lopes
author_role author
dc.contributor.authorlattes.por.fl_str_mv http://lattes.cnpq.br/9412487106628965
dc.contributor.author.fl_str_mv Silva, Taynara Lopes
dc.contributor.advisor1.fl_str_mv Vieira, Paulo Cezar
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/8923844563320377
dc.contributor.authorID.fl_str_mv e222ef86-105c-47f3-b5d1-e50a9702482f
contributor_str_mv Vieira, Paulo Cezar
dc.subject.por.fl_str_mv Produtos naturais
Enzimas
Inibidores enzimáticos
Cerrados
topic Produtos naturais
Enzimas
Inibidores enzimáticos
Cerrados
CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ORGANICA::FISICO-QUIMICA ORGANICA
dc.subject.cnpq.fl_str_mv CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ORGANICA::FISICO-QUIMICA ORGANICA
description This work describes the isolation of bioactive secondary metabolites of the plant species Bowdichia virgilioides in the search for selective inhibitors of cathepsins K, L and V. Cathepsins are enzymes that have as primary function the degradation of proteins in the lysosomes, and are also related to development of diseases such as osteoporosis, rheumatoid arthritis, atherosclerosis and various cancers. This dissertation describes the bioactivity-guided study of the ethanol extracts and fractions obtained from the stems and leaves of B. virgilioides through fluorimetric inhibition assay of the enzymes studied. The extracts of B. virgilioides were subjected to successive fractionations using different chromatographic techniques leading to several pure substances. The isolated substances had their structures elucidated by NMR uni- and bi-dimensional and mass spectrometry. The hexane and ethyl acetate fractions of stem afforded eleven substances: 2 triterpenes, lupeol and lupenona; the mixture of steroids β-sitosterol and stigmasterol; 1 ester derivative of trans pcoumaric acid; 1 furofuran lignan, syringaresinol; 1Benzofuran derivative, bowdenol; 1 coumestrol derivative, 8-methoxycoumestrol, and 3 isoflavones, 7,3'-dihydroxy-4'- methoxyisoflavone, 5,4'-dihydroxy-7'-methoxyisoflavone and 4-hydroxy-7-methoxyisoflavone. All compounds were tested on their ability to inhibit the enzymes at a concentration of 100μM. 8-Methoxycoumestrol showed inhibition superior to 70% for cathepsin V. The potency of this inhibitor was determined and the IC50 value was found to be 17.4 ± 1.0μM for cathepsin V. The ester derivative of trans p-coumaric acid also showed good inhibition above 70% for cathepsin L and V at a concentration of 50μg/mL. So, a series of 8 esters derived from p-hydroxybenzoic acid, p-coumaric acid, cinnamic and ferulic were prepared, and have been evaluated regarding their inhibitory activities of the cathepsins at a concentration of 100μM. n-Octyl pcoumarate ester showed the best percentage inhibition for the three enzymes. The constituents of the hexane fraction of leaves of B. virgilioides were analyzed using the techniques 1H NMR and GC-MS.
publishDate 2014
dc.date.issued.fl_str_mv 2014-03-31
dc.date.accessioned.fl_str_mv 2016-10-04T18:49:43Z
dc.date.available.fl_str_mv 2016-10-04T18:49:43Z
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 SILVA, Taynara Lopes. Estudo químico de Bowdichia virgilioides (Fabaceae) na busca de inibidores seletivos de cisteíno peptidases. 2014. Dissertação (Mestrado em Química) – Universidade Federal de São Carlos, São Carlos, 2014. Disponível em: https://repositorio.ufscar.br/handle/ufscar/7670.
dc.identifier.uri.fl_str_mv https://repositorio.ufscar.br/handle/ufscar/7670
identifier_str_mv SILVA, Taynara Lopes. Estudo químico de Bowdichia virgilioides (Fabaceae) na busca de inibidores seletivos de cisteíno peptidases. 2014. Dissertação (Mestrado em Química) – Universidade Federal de São Carlos, São Carlos, 2014. Disponível em: https://repositorio.ufscar.br/handle/ufscar/7670.
url https://repositorio.ufscar.br/handle/ufscar/7670
dc.language.iso.fl_str_mv por
language por
dc.relation.confidence.fl_str_mv 600
dc.relation.authority.fl_str_mv 74f71c3f-154a-42a0-9eaa-a32f1f60d4c4
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Universidade Federal de São Carlos
Câmpus São Carlos
dc.publisher.program.fl_str_mv Programa de Pós-Graduação em Química - PPGQ
dc.publisher.initials.fl_str_mv UFSCar
publisher.none.fl_str_mv Universidade Federal de São Carlos
Câmpus São Carlos
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instname_str Universidade Federal de São Carlos (UFSCAR)
instacron_str UFSCAR
institution UFSCAR
reponame_str Repositório Institucional da UFSCAR
collection Repositório Institucional da UFSCAR
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