Estudo químico de Bowdichia virgilioides (Fabaceae) na busca de inibidores seletivos de cisteíno peptidases
Autor(a) principal: | |
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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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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:ufscar/7670TElDRU7Dh0EgREUgRElTVFJJQlVJw4fDg08gTsODTy1FWENMVVNJVkEKCkNvbSBhIGFwcmVzZW50YcOnw6NvIGRlc3RhIGxpY2Vuw6dhLCB2b2PDqiAobyBhdXRvciAoZXMpIG91IG8gdGl0dWxhciBkb3MgZGlyZWl0b3MgZGUgYXV0b3IpIGNvbmNlZGUgw6AgVW5pdmVyc2lkYWRlCkZlZGVyYWwgZGUgU8OjbyBDYXJsb3MgbyBkaXJlaXRvIG7Do28tZXhjbHVzaXZvIGRlIHJlcHJvZHV6aXIsICB0cmFkdXppciAoY29uZm9ybWUgZGVmaW5pZG8gYWJhaXhvKSwgZS9vdQpkaXN0cmlidWlyIGEgc3VhIHRlc2Ugb3UgZGlzc2VydGHDp8OjbyAoaW5jbHVpbmRvIG8gcmVzdW1vKSBwb3IgdG9kbyBvIG11bmRvIG5vIGZvcm1hdG8gaW1wcmVzc28gZSBlbGV0csO0bmljbyBlCmVtIHF1YWxxdWVyIG1laW8sIGluY2x1aW5kbyBvcyBmb3JtYXRvcyDDoXVkaW8gb3UgdsOtZGVvLgoKVm9jw6ogY29uY29yZGEgcXVlIGEgVUZTQ2FyIHBvZGUsIHNlbSBhbHRlcmFyIG8gY29udGXDumRvLCB0cmFuc3BvciBhIHN1YSB0ZXNlIG91IGRpc3NlcnRhw6fDo28KcGFyYSBxdWFscXVlciBtZWlvIG91IGZvcm1hdG8gcGFyYSBmaW5zIGRlIHByZXNlcnZhw6fDo28uCgpWb2PDqiB0YW1iw6ltIGNvbmNvcmRhIHF1ZSBhIFVGU0NhciBwb2RlIG1hbnRlciBtYWlzIGRlIHVtYSBjw7NwaWEgYSBzdWEgdGVzZSBvdQpkaXNzZXJ0YcOnw6NvIHBhcmEgZmlucyBkZSBzZWd1cmFuw6dhLCBiYWNrLXVwIGUgcHJlc2VydmHDp8Ojby4KClZvY8OqIGRlY2xhcmEgcXVlIGEgc3VhIHRlc2Ugb3UgZGlzc2VydGHDp8OjbyDDqSBvcmlnaW5hbCBlIHF1ZSB2b2PDqiB0ZW0gbyBwb2RlciBkZSBjb25jZWRlciBvcyBkaXJlaXRvcyBjb250aWRvcwpuZXN0YSBsaWNlbsOnYS4gVm9jw6ogdGFtYsOpbSBkZWNsYXJhIHF1ZSBvIGRlcMOzc2l0byBkYSBzdWEgdGVzZSBvdSBkaXNzZXJ0YcOnw6NvIG7Do28sIHF1ZSBzZWphIGRlIHNldQpjb25oZWNpbWVudG8sIGluZnJpbmdlIGRpcmVpdG9zIGF1dG9yYWlzIGRlIG5pbmd1w6ltLgoKQ2FzbyBhIHN1YSB0ZXNlIG91IGRpc3NlcnRhw6fDo28gY29udGVuaGEgbWF0ZXJpYWwgcXVlIHZvY8OqIG7Do28gcG9zc3VpIGEgdGl0dWxhcmlkYWRlIGRvcyBkaXJlaXRvcyBhdXRvcmFpcywgdm9jw6oKZGVjbGFyYSBxdWUgb2J0ZXZlIGEgcGVybWlzc8OjbyBpcnJlc3RyaXRhIGRvIGRldGVudG9yIGRvcyBkaXJlaXRvcyBhdXRvcmFpcyBwYXJhIGNvbmNlZGVyIMOgIFVGU0NhcgpvcyBkaXJlaXRvcyBhcHJlc2VudGFkb3MgbmVzdGEgbGljZW7Dp2EsIGUgcXVlIGVzc2UgbWF0ZXJpYWwgZGUgcHJvcHJpZWRhZGUgZGUgdGVyY2Vpcm9zIGVzdMOhIGNsYXJhbWVudGUKaWRlbnRpZmljYWRvIGUgcmVjb25oZWNpZG8gbm8gdGV4dG8gb3Ugbm8gY29udGXDumRvIGRhIHRlc2Ugb3UgZGlzc2VydGHDp8OjbyBvcmEgZGVwb3NpdGFkYS4KCkNBU08gQSBURVNFIE9VIERJU1NFUlRBw4fDg08gT1JBIERFUE9TSVRBREEgVEVOSEEgU0lETyBSRVNVTFRBRE8gREUgVU0gUEFUUk9Dw41OSU8gT1UKQVBPSU8gREUgVU1BIEFHw4pOQ0lBIERFIEZPTUVOVE8gT1UgT1VUUk8gT1JHQU5JU01PIFFVRSBOw4NPIFNFSkEgQSBVRlNDYXIsClZPQ8OKIERFQ0xBUkEgUVVFIFJFU1BFSVRPVSBUT0RPUyBFIFFVQUlTUVVFUiBESVJFSVRPUyBERSBSRVZJU8ODTyBDT01PClRBTULDiU0gQVMgREVNQUlTIE9CUklHQcOHw5VFUyBFWElHSURBUyBQT1IgQ09OVFJBVE8gT1UgQUNPUkRPLgoKQSBVRlNDYXIgc2UgY29tcHJvbWV0ZSBhIGlkZW50aWZpY2FyIGNsYXJhbWVudGUgbyBzZXUgbm9tZSAocykgb3UgbyhzKSBub21lKHMpIGRvKHMpCmRldGVudG9yKGVzKSBkb3MgZGlyZWl0b3MgYXV0b3JhaXMgZGEgdGVzZSBvdSBkaXNzZXJ0YcOnw6NvLCBlIG7Do28gZmFyw6EgcXVhbHF1ZXIgYWx0ZXJhw6fDo28sIGFsw6ltIGRhcXVlbGFzCmNvbmNlZGlkYXMgcG9yIGVzdGEgbGljZW7Dp2EuCg==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 |
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por |
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600 |
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74f71c3f-154a-42a0-9eaa-a32f1f60d4c4 |
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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 |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFSCAR instname:Universidade Federal de São Carlos (UFSCAR) instacron:UFSCAR |
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UFSCAR |
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