Síntese de ácidos anacárdicos e análogos, candidatos a inibidores da enzima gliceraldeido-3-fosfato desidrogenase glicossomal de Trypanosoma cruzi
Autor(a) principal: | |
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Data de Publicação: | 2007 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional da UFSCAR |
Texto Completo: | https://repositorio.ufscar.br/handle/ufscar/6400 |
Resumo: | Chagas disease, caused by Trypanosoma cruzi, is endemic in 15 countries in Latin America, including Brazil, and it is estimated that about 16 million people are infected by this protozoan. The enzyme glyceraldehyde-3- phosphato-dehydrogenase (gGAPDH) is one of the nine enzymes involved in the T. cruzi glycolysis and experimentally it was proved that inhibition of this metabolic pathway causes the elimination of trypanosomes in the bloodstream. Among several natural products that have presented interesting inhibitory activity against this enzyme are the anacardic acids, isolated from cashew-nut shells. Many biologic and/or pharmacologic properties have been described for this class of compounds. In this work a serie of anacardic acids and analogues were synthetized and their biological activity evaluated . In total, 23 compounds were prepared and evaluated against T. cruzi gGAPDH and Schistossoma mansoni purine nucleoside phosphorylase (PNP) enzymes. In both cases the most active compound was 6-n-decylsalicylic acid with IC50 of 55 and 30 M respectively. Through the analysis of the experimental results together with the molecular dock studies, it was possible to observe that the size and substituents of alkyl side chain in these compounds can influence the inhibitory activity and the free hydroxyl groups in the ring are essential for the activity. |
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Pereira, Junia MottaCorrêa, Arlene Gonçalveshttp://genos.cnpq.br:12010/dwlattes/owa/prc_imp_cv_int?f_cod=K4781708P5http://lattes.cnpq.br/688258878948279156e8c2c2-445a-45f1-9c59-3ba336f3f4172016-06-02T20:36:13Z2008-08-192016-06-02T20:36:13Z2007-05-18PEREIRA, Junia Motta. Synthesis of anacardic acids and analogues, possible Inhibitors of trypanosoma cruzi glyceraldehyde-3- Phosphato-dehydrogenase enzyme. 2007. 191 f. Dissertação (Mestrado em Ciências Exatas e da Terra) - Universidade Federal de São Carlos, São Carlos, 2007.https://repositorio.ufscar.br/handle/ufscar/6400Chagas disease, caused by Trypanosoma cruzi, is endemic in 15 countries in Latin America, including Brazil, and it is estimated that about 16 million people are infected by this protozoan. The enzyme glyceraldehyde-3- phosphato-dehydrogenase (gGAPDH) is one of the nine enzymes involved in the T. cruzi glycolysis and experimentally it was proved that inhibition of this metabolic pathway causes the elimination of trypanosomes in the bloodstream. Among several natural products that have presented interesting inhibitory activity against this enzyme are the anacardic acids, isolated from cashew-nut shells. Many biologic and/or pharmacologic properties have been described for this class of compounds. In this work a serie of anacardic acids and analogues were synthetized and their biological activity evaluated . In total, 23 compounds were prepared and evaluated against T. cruzi gGAPDH and Schistossoma mansoni purine nucleoside phosphorylase (PNP) enzymes. In both cases the most active compound was 6-n-decylsalicylic acid with IC50 of 55 and 30 M respectively. Through the analysis of the experimental results together with the molecular dock studies, it was possible to observe that the size and substituents of alkyl side chain in these compounds can influence the inhibitory activity and the free hydroxyl groups in the ring are essential for the activity.A doença de Chagas, causada pelo Trypanosoma cruzi, é endêmica em 15 países da América Latina, incluindo o Brasil, e estima-se que cerca de 16 milhões de pessoas estão infectadas por este protozoário. A enzima gliceraldeído-3-fosfato-desidrogenase glicossomal (gGAPDH) é uma das nove enzimas presentes na via glicolítica desse protozoário, e experimentalmente foi comprovado que a inibição dessa via leva à eliminação dos tripanosomas da corrente sanguínea. Dentre diversos produtos naturais que apresentaram atividade inibitória contra esta enzima estão os ácidos anacárdicos, isolados do óleo da castanha de caju. Várias propriedades biológicas e/ou farmacológicas têm sido descritas para esta classe de compostos. O presente trabalho teve como objetivo sintetizar e avaliar a atividade biológica de uma coleção de ácidos anacárdicos e análogos. No total, 23 compostos foram preparados e avaliados com as enzimas gGAPDH de T. cruzi e Purina Nucleosídeo Fosforilase (PNP) de Schistossoma mansoni. Em ambos os casos, o composto mais ativo foi o ácido 6-n-decilsalicílico que apresentou um IC50 de 55 e 30 M, respectivamente. Analisando-se os resultados obtidos, juntamente com estudos de modelagem molecular, observouse que o tamanho e subtituintes na cadeia lateral alquílica podem influenciar na atividade inibitória e que as hidroxilas livres das funções presentes no anel são essenciais para a atividade.Universidade Federal de Sao Carlosapplication/pdfporUniversidade Federal de São CarlosPrograma de Pós-Graduação em Química - PPGQUFSCarBRSíntese orgânicaChagas, Doença deÁcidos anacárdicosGAPDHProdutos naturais. 6. Síntese em fase sólidaCIENCIAS EXATAS E DA TERRA::QUIMICASíntese de ácidos anacárdicos e análogos, candidatos a inibidores da enzima gliceraldeido-3-fosfato desidrogenase glicossomal de Trypanosoma cruziSynthesis of anacardic acids and analogues, possible Inhibitors of trypanosoma cruzi glyceraldehyde-3- Phosphato-dehydrogenase enzymeinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesis-1-1d0f2b9e6-a39b-4adb-8930-18725207ea16info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFSCARinstname:Universidade Federal de São Carlos (UFSCAR)instacron:UFSCARORIGINAL1925.pdfapplication/pdf5727198https://repositorio.ufscar.br/bitstream/ufscar/6400/1/1925.pdf46e27e09d790ee7c1350bedf5b1e7a8fMD51THUMBNAIL1925.pdf.jpg1925.pdf.jpgIM Thumbnailimage/jpeg9548https://repositorio.ufscar.br/bitstream/ufscar/6400/2/1925.pdf.jpg8ebdbe9c5000e7ba78cbecfc8f41ae5bMD52ufscar/64002023-09-18 18:31:11.243oai:repositorio.ufscar.br:ufscar/6400Repositório InstitucionalPUBhttps://repositorio.ufscar.br/oai/requestopendoar:43222023-09-18T18:31:11Repositório Institucional da UFSCAR - Universidade Federal de São Carlos (UFSCAR)false |
dc.title.por.fl_str_mv |
Síntese de ácidos anacárdicos e análogos, candidatos a inibidores da enzima gliceraldeido-3-fosfato desidrogenase glicossomal de Trypanosoma cruzi |
dc.title.alternative.eng.fl_str_mv |
Synthesis of anacardic acids and analogues, possible Inhibitors of trypanosoma cruzi glyceraldehyde-3- Phosphato-dehydrogenase enzyme |
title |
Síntese de ácidos anacárdicos e análogos, candidatos a inibidores da enzima gliceraldeido-3-fosfato desidrogenase glicossomal de Trypanosoma cruzi |
spellingShingle |
Síntese de ácidos anacárdicos e análogos, candidatos a inibidores da enzima gliceraldeido-3-fosfato desidrogenase glicossomal de Trypanosoma cruzi Pereira, Junia Motta Síntese orgânica Chagas, Doença de Ácidos anacárdicos GAPDH Produtos naturais. 6. Síntese em fase sólida CIENCIAS EXATAS E DA TERRA::QUIMICA |
title_short |
Síntese de ácidos anacárdicos e análogos, candidatos a inibidores da enzima gliceraldeido-3-fosfato desidrogenase glicossomal de Trypanosoma cruzi |
title_full |
Síntese de ácidos anacárdicos e análogos, candidatos a inibidores da enzima gliceraldeido-3-fosfato desidrogenase glicossomal de Trypanosoma cruzi |
title_fullStr |
Síntese de ácidos anacárdicos e análogos, candidatos a inibidores da enzima gliceraldeido-3-fosfato desidrogenase glicossomal de Trypanosoma cruzi |
title_full_unstemmed |
Síntese de ácidos anacárdicos e análogos, candidatos a inibidores da enzima gliceraldeido-3-fosfato desidrogenase glicossomal de Trypanosoma cruzi |
title_sort |
Síntese de ácidos anacárdicos e análogos, candidatos a inibidores da enzima gliceraldeido-3-fosfato desidrogenase glicossomal de Trypanosoma cruzi |
author |
Pereira, Junia Motta |
author_facet |
Pereira, Junia Motta |
author_role |
author |
dc.contributor.authorlattes.por.fl_str_mv |
http://lattes.cnpq.br/6882588789482791 |
dc.contributor.author.fl_str_mv |
Pereira, Junia Motta |
dc.contributor.advisor1.fl_str_mv |
Corrêa, Arlene Gonçalves |
dc.contributor.advisor1Lattes.fl_str_mv |
http://genos.cnpq.br:12010/dwlattes/owa/prc_imp_cv_int?f_cod=K4781708P5 |
dc.contributor.authorID.fl_str_mv |
56e8c2c2-445a-45f1-9c59-3ba336f3f417 |
contributor_str_mv |
Corrêa, Arlene Gonçalves |
dc.subject.por.fl_str_mv |
Síntese orgânica Chagas, Doença de Ácidos anacárdicos GAPDH Produtos naturais. 6. Síntese em fase sólida |
topic |
Síntese orgânica Chagas, Doença de Ácidos anacárdicos GAPDH Produtos naturais. 6. Síntese em fase sólida CIENCIAS EXATAS E DA TERRA::QUIMICA |
dc.subject.cnpq.fl_str_mv |
CIENCIAS EXATAS E DA TERRA::QUIMICA |
description |
Chagas disease, caused by Trypanosoma cruzi, is endemic in 15 countries in Latin America, including Brazil, and it is estimated that about 16 million people are infected by this protozoan. The enzyme glyceraldehyde-3- phosphato-dehydrogenase (gGAPDH) is one of the nine enzymes involved in the T. cruzi glycolysis and experimentally it was proved that inhibition of this metabolic pathway causes the elimination of trypanosomes in the bloodstream. Among several natural products that have presented interesting inhibitory activity against this enzyme are the anacardic acids, isolated from cashew-nut shells. Many biologic and/or pharmacologic properties have been described for this class of compounds. In this work a serie of anacardic acids and analogues were synthetized and their biological activity evaluated . In total, 23 compounds were prepared and evaluated against T. cruzi gGAPDH and Schistossoma mansoni purine nucleoside phosphorylase (PNP) enzymes. In both cases the most active compound was 6-n-decylsalicylic acid with IC50 of 55 and 30 M respectively. Through the analysis of the experimental results together with the molecular dock studies, it was possible to observe that the size and substituents of alkyl side chain in these compounds can influence the inhibitory activity and the free hydroxyl groups in the ring are essential for the activity. |
publishDate |
2007 |
dc.date.issued.fl_str_mv |
2007-05-18 |
dc.date.available.fl_str_mv |
2008-08-19 2016-06-02T20:36:13Z |
dc.date.accessioned.fl_str_mv |
2016-06-02T20:36:13Z |
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 |
PEREIRA, Junia Motta. Synthesis of anacardic acids and analogues, possible Inhibitors of trypanosoma cruzi glyceraldehyde-3- Phosphato-dehydrogenase enzyme. 2007. 191 f. Dissertação (Mestrado em Ciências Exatas e da Terra) - Universidade Federal de São Carlos, São Carlos, 2007. |
dc.identifier.uri.fl_str_mv |
https://repositorio.ufscar.br/handle/ufscar/6400 |
identifier_str_mv |
PEREIRA, Junia Motta. Synthesis of anacardic acids and analogues, possible Inhibitors of trypanosoma cruzi glyceraldehyde-3- Phosphato-dehydrogenase enzyme. 2007. 191 f. Dissertação (Mestrado em Ciências Exatas e da Terra) - Universidade Federal de São Carlos, São Carlos, 2007. |
url |
https://repositorio.ufscar.br/handle/ufscar/6400 |
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por |
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info:eu-repo/semantics/openAccess |
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openAccess |
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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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