Busca de inibidores multialvo das enzimas CYP51 e DECR de trypanosoma cruzi para o tratamento da doença de Chagas

Detalhes bibliográficos
Autor(a) principal: Pereira, Ronniery Ilario
Data de Publicação: 2019
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações do LNCC
Texto Completo: https://tede.lncc.br/handle/tede/322
Resumo: Computational techniques for modeling molecules have been shown to be indispensable for the development of new drugs by reducing the cost, time and side effects by making the molecular target of the molecule under study more specific. This methodology is being used in the strategy of repositioning drugs for neglected diseases such as Chagas disease, whose treatment still has many side effects. In this work we aim to search for multi-target inhibitors of the enzymes CYP51 and DECR, considered potential therapeutic targets for the treatment of Chagas disease. Through the molecular docking technique using the Glide software, the mode and affinity of several compounds at the active site of the targets were evaluated. Library of ligands were used, containing molecules approved by the FDA and other compounds synthesized by collaborators such as LASSBio-UFRJ. The compounds cangrelor and bedaquiline showed good values of interaction affinity with the enzymes studied in this work. For the LASSBio database, the compounds LASSBio457, LASSBio460 and LASSBio558 proved to be promising multi-target compounds.
id LNCC_f40e3ae402600ee1ef1b539093e77300
oai_identifier_str oai:tede-server.lncc.br:tede/322
network_acronym_str LNCC
network_name_str Biblioteca Digital de Teses e Dissertações do LNCC
repository_id_str
spelling Dardenne, Laurent EmmanuelGuedes, Isabella AlvimGuedes, Isabella AlvimCustódio, Fábio LimaSodero, Ana Carolina Rennóhttp://lattes.cnpq.br/0269185890336505Pereira, Ronniery Ilario2023-03-08T18:45:10Z2019-09-05PEREIRA, R. I. Busca de inibidores multialvo das enzimas CYP51 e DECR de trypanosoma cruzi para o tratamento da doença de Chagas. 2019. 149 f. Dissertação (Programa de Pós-Graduação em Modelagem Computacional) - Laboratório Nacional de Computação Científica, Petrópolis, 2019.https://tede.lncc.br/handle/tede/322Computational techniques for modeling molecules have been shown to be indispensable for the development of new drugs by reducing the cost, time and side effects by making the molecular target of the molecule under study more specific. This methodology is being used in the strategy of repositioning drugs for neglected diseases such as Chagas disease, whose treatment still has many side effects. In this work we aim to search for multi-target inhibitors of the enzymes CYP51 and DECR, considered potential therapeutic targets for the treatment of Chagas disease. Through the molecular docking technique using the Glide software, the mode and affinity of several compounds at the active site of the targets were evaluated. Library of ligands were used, containing molecules approved by the FDA and other compounds synthesized by collaborators such as LASSBio-UFRJ. The compounds cangrelor and bedaquiline showed good values of interaction affinity with the enzymes studied in this work. For the LASSBio database, the compounds LASSBio457, LASSBio460 and LASSBio558 proved to be promising multi-target compounds.Técnicas computacionais para a modelagem de moléculas têm-se mostrado indispensáveis para o desenvolvimento de novos medicamentos ao reduzir o custo, tempo e efeitos colaterais ao tornar mais específico o alvo molecular da molécula em estudo. Essa metodologia está sendo utilizada na estratégia de reposicionamento de fármacos para doenças negligenciadas como a doença de Chagas, cujo tratamento ainda apresenta muitos efeitos colaterais. Neste trabalho temos como objetivo a busca por inibidores multialvo das enzimas CYP51 e DECR, consideradas potenciais alvos terapêuticos para o tratamento da doença de Chagas. Por meio da técnica de atracamento molecular utilizando o programa Glide, o modo e afinidade de diversos compostos no sítio ativo dos alvos foram avaliados. Foram utilizados bancos de ligantes, contendo moléculas aprovadas pelo FDA e outros compostos sintetizados por colaboradores como o LASSBio- UFRJ. Os compostos cangrelor e bedaquiline apresentaram bons valores de afinidade de interação com as enzimas estudadas neste trabalho. Para o banco de dados do LASSBio, os compostos LASSBio457, LASSBio460 e LASSBio558 se mostraram compostos multialvo promissores.Submitted by Patrícia Vieira Silva (library@lncc.br) on 2023-03-08T18:44:45Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_Final_Ronniery_Pereira.pdf: 4302328 bytes, checksum: 9e562f79397a792a61c611638b28ebdb (MD5)Approved for entry into archive by Patrícia Vieira Silva (library@lncc.br) on 2023-03-08T18:44:57Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_Final_Ronniery_Pereira.pdf: 4302328 bytes, checksum: 9e562f79397a792a61c611638b28ebdb (MD5)Made available in DSpace on 2023-03-08T18:45:10Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertacao_Final_Ronniery_Pereira.pdf: 4302328 bytes, checksum: 9e562f79397a792a61c611638b28ebdb (MD5) Previous issue date: 2019-09-05Conselho Nacional de Desenvolvimento Científico e Tecnológicoapplication/pdfhttp://tede-server.lncc.br:8080/retrieve/1238/Dissertacao_Final_Ronniery_Pereira.pdf.jpgporLaboratório Nacional de Computação CientíficaPrograma de Pós-Graduação em Modelagem ComputacionalLNCCBrasilCoordenação de Pós-Graduação e Aperfeiçoamento (COPGA)http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessReposicionamento de fármacosChagas, Doença deFamília 51 do Citocromo P450Ancoragem molecularDocking MolecularCNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIABusca de inibidores multialvo das enzimas CYP51 e DECR de trypanosoma cruzi para o tratamento da doença de Chagasinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisreponame:Biblioteca Digital de Teses e Dissertações do LNCCinstname:Laboratório Nacional de Computação Científica (LNCC)instacron:LNCCLICENSElicense.txtlicense.txttext/plain; charset=utf-82165http://tede-server.lncc.br:8080/tede/bitstream/tede/322/1/license.txtbd3efa91386c1718a7f26a329fdcb468MD51CC-LICENSElicense_urllicense_urltext/plain; charset=utf-849http://tede-server.lncc.br:8080/tede/bitstream/tede/322/2/license_url4afdbb8c545fd630ea7db775da747b2fMD52license_textlicense_texttext/html; charset=utf-80http://tede-server.lncc.br:8080/tede/bitstream/tede/322/3/license_textd41d8cd98f00b204e9800998ecf8427eMD53license_rdflicense_rdfapplication/rdf+xml; charset=utf-80http://tede-server.lncc.br:8080/tede/bitstream/tede/322/4/license_rdfd41d8cd98f00b204e9800998ecf8427eMD54ORIGINALDissertacao_Final_Ronniery_Pereira.pdfDissertacao_Final_Ronniery_Pereira.pdfapplication/pdf4302328http://tede-server.lncc.br:8080/tede/bitstream/tede/322/5/Dissertacao_Final_Ronniery_Pereira.pdf9e562f79397a792a61c611638b28ebdbMD55TEXTDissertacao_Final_Ronniery_Pereira.pdf.txtDissertacao_Final_Ronniery_Pereira.pdf.txttext/plain167770http://tede-server.lncc.br:8080/tede/bitstream/tede/322/6/Dissertacao_Final_Ronniery_Pereira.pdf.txt2744116b6b7eea9030460f990f1b1e40MD56THUMBNAILDissertacao_Final_Ronniery_Pereira.pdf.jpgDissertacao_Final_Ronniery_Pereira.pdf.jpgimage/jpeg2652http://tede-server.lncc.br:8080/tede/bitstream/tede/322/7/Dissertacao_Final_Ronniery_Pereira.pdf.jpg13f7b13da16f1413bb183edfea5c24d6MD57tede/3222023-06-02 12:06:16.72oai:tede-server.lncc.br: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Biblioteca Digital de Teses e Dissertaçõeshttps://tede.lncc.br/PUBhttps://tede.lncc.br/oai/requestlibrary@lncc.br||library@lncc.bropendoar:2023-06-02T15:06:16Biblioteca Digital de Teses e Dissertações do LNCC - Laboratório Nacional de Computação Científica (LNCC)false
dc.title.por.fl_str_mv Busca de inibidores multialvo das enzimas CYP51 e DECR de trypanosoma cruzi para o tratamento da doença de Chagas
title Busca de inibidores multialvo das enzimas CYP51 e DECR de trypanosoma cruzi para o tratamento da doença de Chagas
spellingShingle Busca de inibidores multialvo das enzimas CYP51 e DECR de trypanosoma cruzi para o tratamento da doença de Chagas
Pereira, Ronniery Ilario
Reposicionamento de fármacos
Chagas, Doença de
Família 51 do Citocromo P450
Ancoragem molecular
Docking Molecular
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
title_short Busca de inibidores multialvo das enzimas CYP51 e DECR de trypanosoma cruzi para o tratamento da doença de Chagas
title_full Busca de inibidores multialvo das enzimas CYP51 e DECR de trypanosoma cruzi para o tratamento da doença de Chagas
title_fullStr Busca de inibidores multialvo das enzimas CYP51 e DECR de trypanosoma cruzi para o tratamento da doença de Chagas
title_full_unstemmed Busca de inibidores multialvo das enzimas CYP51 e DECR de trypanosoma cruzi para o tratamento da doença de Chagas
title_sort Busca de inibidores multialvo das enzimas CYP51 e DECR de trypanosoma cruzi para o tratamento da doença de Chagas
author Pereira, Ronniery Ilario
author_facet Pereira, Ronniery Ilario
author_role author
dc.contributor.advisor1.fl_str_mv Dardenne, Laurent Emmanuel
dc.contributor.advisor2.fl_str_mv Guedes, Isabella Alvim
dc.contributor.referee1.fl_str_mv Guedes, Isabella Alvim
dc.contributor.referee2.fl_str_mv Custódio, Fábio Lima
dc.contributor.referee3.fl_str_mv Sodero, Ana Carolina Rennó
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/0269185890336505
dc.contributor.author.fl_str_mv Pereira, Ronniery Ilario
contributor_str_mv Dardenne, Laurent Emmanuel
Guedes, Isabella Alvim
Guedes, Isabella Alvim
Custódio, Fábio Lima
Sodero, Ana Carolina Rennó
dc.subject.por.fl_str_mv Reposicionamento de fármacos
Chagas, Doença de
Família 51 do Citocromo P450
Ancoragem molecular
Docking Molecular
topic Reposicionamento de fármacos
Chagas, Doença de
Família 51 do Citocromo P450
Ancoragem molecular
Docking Molecular
CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS BIOLOGICAS::FARMACOLOGIA
description Computational techniques for modeling molecules have been shown to be indispensable for the development of new drugs by reducing the cost, time and side effects by making the molecular target of the molecule under study more specific. This methodology is being used in the strategy of repositioning drugs for neglected diseases such as Chagas disease, whose treatment still has many side effects. In this work we aim to search for multi-target inhibitors of the enzymes CYP51 and DECR, considered potential therapeutic targets for the treatment of Chagas disease. Through the molecular docking technique using the Glide software, the mode and affinity of several compounds at the active site of the targets were evaluated. Library of ligands were used, containing molecules approved by the FDA and other compounds synthesized by collaborators such as LASSBio-UFRJ. The compounds cangrelor and bedaquiline showed good values of interaction affinity with the enzymes studied in this work. For the LASSBio database, the compounds LASSBio457, LASSBio460 and LASSBio558 proved to be promising multi-target compounds.
publishDate 2019
dc.date.issued.fl_str_mv 2019-09-05
dc.date.accessioned.fl_str_mv 2023-03-08T18:45:10Z
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, R. I. Busca de inibidores multialvo das enzimas CYP51 e DECR de trypanosoma cruzi para o tratamento da doença de Chagas. 2019. 149 f. Dissertação (Programa de Pós-Graduação em Modelagem Computacional) - Laboratório Nacional de Computação Científica, Petrópolis, 2019.
dc.identifier.uri.fl_str_mv https://tede.lncc.br/handle/tede/322
identifier_str_mv PEREIRA, R. I. Busca de inibidores multialvo das enzimas CYP51 e DECR de trypanosoma cruzi para o tratamento da doença de Chagas. 2019. 149 f. Dissertação (Programa de Pós-Graduação em Modelagem Computacional) - Laboratório Nacional de Computação Científica, Petrópolis, 2019.
url https://tede.lncc.br/handle/tede/322
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Laboratório Nacional de Computação Científica
dc.publisher.program.fl_str_mv Programa de Pós-Graduação em Modelagem Computacional
dc.publisher.initials.fl_str_mv LNCC
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv Coordenação de Pós-Graduação e Aperfeiçoamento (COPGA)
publisher.none.fl_str_mv Laboratório Nacional de Computação Científica
dc.source.none.fl_str_mv reponame:Biblioteca Digital de Teses e Dissertações do LNCC
instname:Laboratório Nacional de Computação Científica (LNCC)
instacron:LNCC
instname_str Laboratório Nacional de Computação Científica (LNCC)
instacron_str LNCC
institution LNCC
reponame_str Biblioteca Digital de Teses e Dissertações do LNCC
collection Biblioteca Digital de Teses e Dissertações do LNCC
bitstream.url.fl_str_mv http://tede-server.lncc.br:8080/tede/bitstream/tede/322/1/license.txt
http://tede-server.lncc.br:8080/tede/bitstream/tede/322/2/license_url
http://tede-server.lncc.br:8080/tede/bitstream/tede/322/3/license_text
http://tede-server.lncc.br:8080/tede/bitstream/tede/322/4/license_rdf
http://tede-server.lncc.br:8080/tede/bitstream/tede/322/5/Dissertacao_Final_Ronniery_Pereira.pdf
http://tede-server.lncc.br:8080/tede/bitstream/tede/322/6/Dissertacao_Final_Ronniery_Pereira.pdf.txt
http://tede-server.lncc.br:8080/tede/bitstream/tede/322/7/Dissertacao_Final_Ronniery_Pereira.pdf.jpg
bitstream.checksum.fl_str_mv bd3efa91386c1718a7f26a329fdcb468
4afdbb8c545fd630ea7db775da747b2f
d41d8cd98f00b204e9800998ecf8427e
d41d8cd98f00b204e9800998ecf8427e
9e562f79397a792a61c611638b28ebdb
2744116b6b7eea9030460f990f1b1e40
13f7b13da16f1413bb183edfea5c24d6
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
MD5
MD5
MD5
MD5
repository.name.fl_str_mv Biblioteca Digital de Teses e Dissertações do LNCC - Laboratório Nacional de Computação Científica (LNCC)
repository.mail.fl_str_mv library@lncc.br||library@lncc.br
_version_ 1797683219774046208