Estudos estruturais de compostos de telúrio e de docking em catepsinas B, K, L, S
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Tipo de documento: | Tese |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFSCAR |
Texto Completo: | https://repositorio.ufscar.br/handle/ufscar/6262 |
Resumo: | Cathepsins are lysosomal cysteine proteases responsible for protein turnover in our organism. In non-lysosomal environment they are related to a number of diseases such as cancer, Alzheimer, autoimmune diseases and osteoporosis. Tellurium compounds have proved to be promising therapeutic agents against these diseases due to inhibition of the proteases through the formation of a Te S covalent bond with the sulfur of a catalytic cysteine. In this work the crystal and molecular structures of compounds (ptol)Te[C(H)=C(Cl)Ph]X2 (X = Cl, Br, I), butyldiiodo[(1Z)-(2- iodopent-1-en-yl)-4- tellane and their docking in Catepsine B are described. The results showed that these compounds, whose activity has not been measured, should have an inhibitory activity very similar to that of a known compound with a close structure. Moreover, it is shown that the substitution of a phenyl group for an aliphatic one should not have any influence on the activity of these kind of compounds. Also the structures of a series of dipnones were determined which were used as basis for the molecular modeling of others that could not be crystallized and for the docking studies in catepsins B, K, L and S. The results allowed establishing a model that explains their different inhibitory activities. |
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Maganhi, Stella HernandezSchpector, Júlio Zukermanhttp://lattes.cnpq.br/4252331837170383http://lattes.cnpq.br/1720675268286912e6f9cd88-ef13-4c2e-b0af-652d019ddf882016-06-02T20:34:42Z2013-06-072016-06-02T20:34:42Z2013-03-28https://repositorio.ufscar.br/handle/ufscar/6262Cathepsins are lysosomal cysteine proteases responsible for protein turnover in our organism. In non-lysosomal environment they are related to a number of diseases such as cancer, Alzheimer, autoimmune diseases and osteoporosis. Tellurium compounds have proved to be promising therapeutic agents against these diseases due to inhibition of the proteases through the formation of a Te S covalent bond with the sulfur of a catalytic cysteine. In this work the crystal and molecular structures of compounds (ptol)Te[C(H)=C(Cl)Ph]X2 (X = Cl, Br, I), butyldiiodo[(1Z)-(2- iodopent-1-en-yl)-4- tellane and their docking in Catepsine B are described. The results showed that these compounds, whose activity has not been measured, should have an inhibitory activity very similar to that of a known compound with a close structure. Moreover, it is shown that the substitution of a phenyl group for an aliphatic one should not have any influence on the activity of these kind of compounds. Also the structures of a series of dipnones were determined which were used as basis for the molecular modeling of others that could not be crystallized and for the docking studies in catepsins B, K, L and S. The results allowed establishing a model that explains their different inhibitory activities.As catepsinas são cisteíno proteases lisossômicas presentes no nosso organismo. Quando em ambiente não lisossômico, estão relacionadas a uma série de doenças como câncer, Alzheimer, doenças autoimunes e osteoporose. Neste contexto, compostos de telúrio têm sido promissores agentes terapêuticos contra estas doenças por apresentarem ação inibitória das catepsinas. Isso ocorre devido à formação de uma ligação covalente entre telúrio e o enxofre da cisteína catalítica. Neste trabalho são descritas as estruturas cristalinas e moleculares dos compostos (ptol)Te[C(H)=C(Cl)Ph]X2 (X = Cl, Br, I), butildiiodo[(1Z)-(2-iodopent-1-em-1-il) 4- telano, e o docking destes compostos em Catepsina B. Os resultados mostram que estes compostos, cujas atividades não foram medidas, poderão apresentar atividades inibitórias semelhantes à de um composto de estrutura similar e com atividade conhecida. Mais ainda, foi mostrado que a substituição de um grupo fenila por um grupo alifático não deverá ter influência na atividade deste tipo de compostos. Foram também determinadas as estruturas cristalinas e moleculares de três dipnonas. Estas estruturas serviram de base para a modelagem das estruturas de outros compostos que não puderam ser cristalizados e para a realização de docking nas catepsinas B, K, L, e S. Foi então estabelecido um modelo para explicar as diferentes atividades inibitórias dos compostos de telúrio.Universidade Federal de Minas Geraisapplication/pdfporUniversidade Federal de São CarlosPrograma de Pós-Graduação em Química - PPGQUFSCarBRCristalografiaDockingTelúrioRaios xCatepsinasModelagem molecularCIENCIAS EXATAS E DA TERRA::QUIMICAEstudos estruturais de compostos de telúrio e de docking em catepsinas B, K, L, Sinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesis-1-1e0a7cf72-f4fb-48f4-93c2-3e7bc492b3cbinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFSCARinstname:Universidade Federal de São Carlos (UFSCAR)instacron:UFSCARORIGINAL5168.pdfapplication/pdf8720586https://repositorio.ufscar.br/bitstream/ufscar/6262/1/5168.pdf0dc0ddbacccaf3e2f1fcfb515b343484MD51TEXT5168.pdf.txt5168.pdf.txtExtracted texttext/plain0https://repositorio.ufscar.br/bitstream/ufscar/6262/4/5168.pdf.txtd41d8cd98f00b204e9800998ecf8427eMD54THUMBNAIL5168.pdf.jpg5168.pdf.jpgIM Thumbnailimage/jpeg8891https://repositorio.ufscar.br/bitstream/ufscar/6262/5/5168.pdf.jpga13401d116dc7253940c615c79b207a9MD55ufscar/62622023-09-18 18:30:35.998oai:repositorio.ufscar.br:ufscar/6262Repositório InstitucionalPUBhttps://repositorio.ufscar.br/oai/requestopendoar:43222023-09-18T18:30:35Repositório Institucional da UFSCAR - Universidade Federal de São Carlos (UFSCAR)false |
dc.title.por.fl_str_mv |
Estudos estruturais de compostos de telúrio e de docking em catepsinas B, K, L, S |
title |
Estudos estruturais de compostos de telúrio e de docking em catepsinas B, K, L, S |
spellingShingle |
Estudos estruturais de compostos de telúrio e de docking em catepsinas B, K, L, S Maganhi, Stella Hernandez Cristalografia Docking Telúrio Raios x Catepsinas Modelagem molecular CIENCIAS EXATAS E DA TERRA::QUIMICA |
title_short |
Estudos estruturais de compostos de telúrio e de docking em catepsinas B, K, L, S |
title_full |
Estudos estruturais de compostos de telúrio e de docking em catepsinas B, K, L, S |
title_fullStr |
Estudos estruturais de compostos de telúrio e de docking em catepsinas B, K, L, S |
title_full_unstemmed |
Estudos estruturais de compostos de telúrio e de docking em catepsinas B, K, L, S |
title_sort |
Estudos estruturais de compostos de telúrio e de docking em catepsinas B, K, L, S |
author |
Maganhi, Stella Hernandez |
author_facet |
Maganhi, Stella Hernandez |
author_role |
author |
dc.contributor.authorlattes.por.fl_str_mv |
http://lattes.cnpq.br/1720675268286912 |
dc.contributor.author.fl_str_mv |
Maganhi, Stella Hernandez |
dc.contributor.advisor1.fl_str_mv |
Schpector, Júlio Zukerman |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/4252331837170383 |
dc.contributor.authorID.fl_str_mv |
e6f9cd88-ef13-4c2e-b0af-652d019ddf88 |
contributor_str_mv |
Schpector, Júlio Zukerman |
dc.subject.por.fl_str_mv |
Cristalografia Docking Telúrio Raios x Catepsinas Modelagem molecular |
topic |
Cristalografia Docking Telúrio Raios x Catepsinas Modelagem molecular CIENCIAS EXATAS E DA TERRA::QUIMICA |
dc.subject.cnpq.fl_str_mv |
CIENCIAS EXATAS E DA TERRA::QUIMICA |
description |
Cathepsins are lysosomal cysteine proteases responsible for protein turnover in our organism. In non-lysosomal environment they are related to a number of diseases such as cancer, Alzheimer, autoimmune diseases and osteoporosis. Tellurium compounds have proved to be promising therapeutic agents against these diseases due to inhibition of the proteases through the formation of a Te S covalent bond with the sulfur of a catalytic cysteine. In this work the crystal and molecular structures of compounds (ptol)Te[C(H)=C(Cl)Ph]X2 (X = Cl, Br, I), butyldiiodo[(1Z)-(2- iodopent-1-en-yl)-4- tellane and their docking in Catepsine B are described. The results showed that these compounds, whose activity has not been measured, should have an inhibitory activity very similar to that of a known compound with a close structure. Moreover, it is shown that the substitution of a phenyl group for an aliphatic one should not have any influence on the activity of these kind of compounds. Also the structures of a series of dipnones were determined which were used as basis for the molecular modeling of others that could not be crystallized and for the docking studies in catepsins B, K, L and S. The results allowed establishing a model that explains their different inhibitory activities. |
publishDate |
2013 |
dc.date.available.fl_str_mv |
2013-06-07 2016-06-02T20:34:42Z |
dc.date.issued.fl_str_mv |
2013-03-28 |
dc.date.accessioned.fl_str_mv |
2016-06-02T20:34:42Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/doctoralThesis |
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doctoralThesis |
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publishedVersion |
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https://repositorio.ufscar.br/handle/ufscar/6262 |
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https://repositorio.ufscar.br/handle/ufscar/6262 |
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por |
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openAccess |
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application/pdf |
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Universidade Federal de São Carlos |
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Programa de Pós-Graduação em Química - PPGQ |
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UFSCar |
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BR |
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Universidade Federal de São Carlos |
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