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| DC Field | Value | Language |
|---|---|---|
| dc.contributor.author | Santos, Paulo Pitasse | |
| dc.date.accessioned | 2023-12-22T03:04:07Z | - |
| dc.date.available | 2023-12-22T03:04:07Z | - |
| dc.date.issued | 2017-02-20 | |
| dc.identifier.citation | SANTOS, Paulo Pitasse. Planejamento, síntese e avaliação de derivados 1,2,4-oxadiazólicos com potencial atividade tripanocida. 2017. 156 f. Dissertação (Mestrado em Química) - Instituto de Ciências Exatas, Universidade Federal Rural do Rio de Janeiro, Seropédica - RJ, 2017. | por |
| dc.identifier.uri | https://rima.ufrrj.br/jspui/handle/20.500.14407/14657 | - |
| dc.description.abstract | A doença de Chagas foi estudada e descrita pelo médico sanitarista e cientista brasileiro Carlos Chagas, em 1909. É causada pelo protozoário Trypanossoma cruzi, apresentando manifestações clínicas complexas. No entanto, desde sua descoberta, pouco se avançou no tratamento quimioterápico da doença de Chagas, sendo o fármaco disponível (benzonidazol) pouco eficiente e associado à manifestação de diversos efeitos colaterais. A partir do conhecimento da atividade antiparasitária da amida natural piperina, este trabalho focou-se na proposição de novas moléculas estruturalmente semelhantes com potencial tripanocida. A partir dos princípios do bioisosterismo, foi proposta uma série de novos 1,2,4-oxadiazóis diferentemente substituídos. Sua síntese foi concebida partir dos ácidos 3-arilacrílicos correspondentes, obtendo-se os respectivos cloretos de acila, através da reação com cloreto de oxalila. A etapa posterior envolve a O-acilação da benzamidoxima adequadamente substituída, seguida do fechamento do anel oxadiazólico, que se dá em em suporte sólido (sílica-gel) empregando-se irradiação de micro-ondas. A caracterização dos produtos foi feita através de ponto de fusão, RMN 1H e 13C, espectrometria no infravermelho e espectrometria de massas de alta e baixa resolução. O presente trabalho ainda traz informações quanto ao perfil de atividade biológica das moléculas sintetizadas frente a formas epimastigotas do protozoário Trypanosoma cruzi e frente a células primárias de mamíferos, permitindo que se calculasse o seu índice de seletividade. Investigações quanto a possíveis mecanismos de ação dos derivados sobre o T. cruzi indicam não haver influências sobre a ação enzimática da protease cruzaína, sobre o ciclo celular do parasito, nem sobre a biossíntese de esteróis de membrana, catalisada pela enzima CYP51. A metodologia química desenvolvida poderá ser aplicada na síntese de outros análogos. As perspectivas deste trabalho incluem ainda a avaliação biológica frente a formas amastigota e tripomastigota do parasito | por |
| dc.description.sponsorship | CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico | por |
| dc.format | application/pdf | * |
| dc.language | por | por |
| dc.publisher | Universidade Federal Rural do Rio de Janeiro | por |
| dc.rights | Acesso Aberto | por |
| dc.subject | solid phase synthesis | eng |
| dc.subject | atiprotozoan | eng |
| dc.subject | 1,2,4-oxadiazole | eng |
| dc.subject | bioisosterism | eng |
| dc.subject | síntese em fase sólida | por |
| dc.subject | antiprotozoário | por |
| dc.subject | 1,2,4-oxadiazol | por |
| dc.subject | bioisosterismo | por |
| dc.title | Planejamento, síntese e avaliação de derivados 1,2,4-oxadiazólicos com potencial atividade tripanocida | por |
| dc.title.alternative | Planning, synthesis and evaluation of potentially tripanocidal 1,2,4-oxadiazolic derivatives | eng |
| dc.type | Dissertação | por |
| dc.description.abstractOther | Chagas disease was studied and described by the Brazilian sanitarist and physician Carlos Chagas in 1909. It is caused by the protozoan Trypanosoma cruzi and presents complex clinical manifestations. However, since its discovery, little progress has been made in the chemotherapeutic treatment of Chagas' disease. The only available drug for its treatment (benzonidazole) is not completely efficient and is associated with the development of several side effects. From the knowledge of the antiparasitic activity of the natural amidic alkaloid piperine, this work focused on the proposition of new structurally-similar molecules with trypanocidal potential. From the principles of bioisosterism, a series of new 1,2,4-oxadiazoles were proposed. Its synthesis was designed from the corresponding 3-arylacrylic acids to give the respective acyl chlorides by reaction with oxalyl chloride. The subsequent step involves O-acylation of the properly substituted benzamidoxime following the cyclization reaction of the oxadiazolic ring, which occurs in solid support (silica gel) using microwave irradiation. The characterization of the products was done by determination of melting points, 1H and 13C NMR, infrared espectrometry and high and low resolution mass spectrometry. The present work also presents information about the biological activity profile of the molecules synthesized against epimastigote forms of the T. cruzi protozoan and against primary mammalian cells, allowing the calculation of their selectivity indexes. Investigations about the possible mechanisms of action of the derivatives on T. cruzi indicate that there are no influences on the enzymatic action of the protease cruazain, on the cell cycle of the parasite or on the biosynthesis of membrane sterols catalyzed by the enzyme CYP51. The developed sinthetic methodology can be applied in the expansion of the series of analogues derivatives. The perspectives of this work also include the biological evaluation against amastigote and trypomastigote forms of the parasite. | eng |
| dc.contributor.advisor1 | Lima, Marco Edilson Freire de | |
| dc.contributor.advisor1ID | 880.202.667-04 | por |
| dc.contributor.advisor1Lattes | http://lattes.cnpq.br/8392420706762318 | por |
| dc.contributor.advisor-co1 | Santiago, Vitor Sueth | |
| dc.contributor.advisor-co1ID | 116.893.177-01 | por |
| dc.contributor.advisor-co1Lattes | http://lattes.cnpq.br/7873681582100547 | por |
| dc.contributor.referee1 | Trossini, Gustavo Henrique Goulart | |
| dc.contributor.referee2 | Guedes, Herbert Leonel M. | |
| dc.creator.ID | 120.854.447-09 | por |
| dc.creator.Lattes | http://lattes.cnpq.br/1280725643158086 | por |
| dc.publisher.country | Brasil | por |
| dc.publisher.department | Instituto de Ciências Exatas | por |
| dc.publisher.initials | UFRRJ | por |
| dc.publisher.program | Programa de Pós-Graduação em Química | por |
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Acesso em 24 de abril de 2016. https://www.scoppus.com - Pesquisa na base de dados com o termo "Trypanosoma cruzi" junto com os respectivos nomes dos alvos. | por |
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