Hybrids of ImatinibwithQuinoline: Synthesis,Antimyeloproliferative Activity Evaluation, and Molecular Docking

Detalhes bibliográficos
Autor(a) principal: Santos, Carine
Data de Publicação: 2022
Outros Autores: Pimentel, Luiz, Canzian, Henayle, Oliveira, Andressa, Junior, Floriano, Dantas, Rafael, Hoelz, Lucas, Marinho, Debora, Cunha, Anna, Bastos, Monica, Boechat, Nubia
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/55969
Resumo: Fundação Oswaldo Cruz. Instituto de Tecnologia em Farmacos-Farmanguinhos. Laboratório de Sintese de Farmacos-LASFAR. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas–ICB. Programa de Pós-graduação em Farmacologia e Química Medicinal. Rio de Janeiro, RJ Brasil.
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spelling Santos, CarinePimentel, LuizCanzian, HenayleOliveira, AndressaJunior, FlorianoDantas, RafaelHoelz, LucasMarinho, DeboraCunha, AnnaBastos, MonicaBoechat, Nubia2022-12-15T16:03:06Z2022-12-15T16:03:06Z2022SANTOS, Carine et al. Hybrids of Imatinib with Quinoline: Synthesis, Antimyeloproliferative Activity Evaluation, and Molecular Docking. Pharmaceuticals, v.15, 309, p. 1 - 24, Mar. 2022.1999-4923https://www.arca.fiocruz.br/handle/icict/5596910.3390/ ph15030309engMDPICâncerImatinibePAPPQuinolina1,2,3-triazolInibidores de tirosina quinaseCancerImatinibPAPPQuinoline1,2,3-triazoleTyrosine kinase inhibitorsHybrids of ImatinibwithQuinoline: Synthesis,Antimyeloproliferative Activity Evaluation, and Molecular Dockinginfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto de Tecnologia em Farmacos-Farmanguinhos. Laboratório de Sintese de Farmacos-LASFAR. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas–ICB. Programa de Pós-graduação em Farmacologia e Química Medicinal. Rio de Janeiro, RJ Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Farmacos-Farmanguinhos. Laboratório de Sintese de Farmacos-LASFAR. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Farmacos-Farmanguinhos. Laboratório de Sintese de Farmacos-LASFAR. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Farmacos-Farmanguinhos. Laboratório de Sintese de Farmacos-LASFAR. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas–ICB. Programa de Pós-graduação em Farmacologia e Química Medicinal. Rio de Janeiro, RJ Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica Experimental e Computacional de Fármacos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica Experimental e Computacional de Fármacos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Farmacos-Farmanguinhos. Laboratório de Sintese de Farmacos-LASFAR. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Farmacos-Farmanguinhos. Laboratório de Sintese de Farmacos-LASFAR. Rio de Janeiro, RJ, Brasil.Universidade Federal Fluminense. Departamento de Química Orgânica, Campus do Valonguinho. Niterói, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Farmacos-Farmanguinhos. Laboratório de Sintese de Farmacos-LASFAR. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas–ICB. Programa de Pós-graduação em Farmacologia e Química Medicinal. Rio de Janeiro, RJ Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Farmacos-Farmanguinhos. Laboratório de Sintese de Farmacos-LASFAR. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas–ICB. Programa de Pós-graduação em Farmacologia e Química Medicinal. Rio de Janeiro, RJ Brasil.Imatinib (IMT) is the first-in-class BCR-ABL commercial tyrosine kinase inhibitor (TKI). However, the resistance and toxicity associated with the use of IMT highlight the importance of the search for new TKIs. In this context, heterocyclic systems, such as quinoline, which is present as a pharmacophore in the structure of the TKI inhibitor bosutinib (BST), have been widely applied. Thus, this work aimed to obtain new hybrids of imatinib containing quinoline moieties and evaluate them against K562 cells. The compounds were synthesized with a high purity degree. Among the produced molecules, the inhibitor 4-methyl-N3-(4-(pyridin-3-yl)pyrimidin-2-yl)-N1-(quinolin-4-yl)benzene- 1,3-diamine (2g) showed a suitable reduction in cell viability, with a CC50 value of 0.9 M (IMT, CC50 = 0.08 M). Molecular docking results suggest that the interaction between the most active inhibitor 2g and the BCR-ABL1 enzyme occurs at the bosutinib binding site through a competitive inhibition mechanism. Despite being less potent and selective than IMT, 2g is a suitable prototype for use in the search for new drugs against chronic myeloid leukemia (CML), especially in patients with acquired resistance to IMT.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/55969/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALFlorianoJunior_RafaelDantas_etal_IOC_2022.pdfFlorianoJunior_RafaelDantas_etal_IOC_2022.pdfapplication/pdf3961622https://www.arca.fiocruz.br/bitstream/icict/55969/2/FlorianoJunior_RafaelDantas_etal_IOC_2022.pdf5ef551725d0df0598d69bb29a7ee3739MD52icict/559692023-09-04 11:03:01.946oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-09-04T14:03:01Repositório Institucional da FIOCRUZ (ARCA) - 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dc.title.en_US.fl_str_mv Hybrids of ImatinibwithQuinoline: Synthesis,Antimyeloproliferative Activity Evaluation, and Molecular Docking
title Hybrids of ImatinibwithQuinoline: Synthesis,Antimyeloproliferative Activity Evaluation, and Molecular Docking
spellingShingle Hybrids of ImatinibwithQuinoline: Synthesis,Antimyeloproliferative Activity Evaluation, and Molecular Docking
Santos, Carine
Câncer
Imatinibe
PAPP
Quinolina
1,2,3-triazol
Inibidores de tirosina quinase
Cancer
Imatinib
PAPP
Quinoline
1,2,3-triazole
Tyrosine kinase inhibitors
title_short Hybrids of ImatinibwithQuinoline: Synthesis,Antimyeloproliferative Activity Evaluation, and Molecular Docking
title_full Hybrids of ImatinibwithQuinoline: Synthesis,Antimyeloproliferative Activity Evaluation, and Molecular Docking
title_fullStr Hybrids of ImatinibwithQuinoline: Synthesis,Antimyeloproliferative Activity Evaluation, and Molecular Docking
title_full_unstemmed Hybrids of ImatinibwithQuinoline: Synthesis,Antimyeloproliferative Activity Evaluation, and Molecular Docking
title_sort Hybrids of ImatinibwithQuinoline: Synthesis,Antimyeloproliferative Activity Evaluation, and Molecular Docking
author Santos, Carine
author_facet Santos, Carine
Pimentel, Luiz
Canzian, Henayle
Oliveira, Andressa
Junior, Floriano
Dantas, Rafael
Hoelz, Lucas
Marinho, Debora
Cunha, Anna
Bastos, Monica
Boechat, Nubia
author_role author
author2 Pimentel, Luiz
Canzian, Henayle
Oliveira, Andressa
Junior, Floriano
Dantas, Rafael
Hoelz, Lucas
Marinho, Debora
Cunha, Anna
Bastos, Monica
Boechat, Nubia
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Santos, Carine
Pimentel, Luiz
Canzian, Henayle
Oliveira, Andressa
Junior, Floriano
Dantas, Rafael
Hoelz, Lucas
Marinho, Debora
Cunha, Anna
Bastos, Monica
Boechat, Nubia
dc.subject.other.en_US.fl_str_mv Câncer
Imatinibe
PAPP
Quinolina
1,2,3-triazol
Inibidores de tirosina quinase
topic Câncer
Imatinibe
PAPP
Quinolina
1,2,3-triazol
Inibidores de tirosina quinase
Cancer
Imatinib
PAPP
Quinoline
1,2,3-triazole
Tyrosine kinase inhibitors
dc.subject.en.en_US.fl_str_mv Cancer
Imatinib
PAPP
Quinoline
1,2,3-triazole
Tyrosine kinase inhibitors
description Fundação Oswaldo Cruz. Instituto de Tecnologia em Farmacos-Farmanguinhos. Laboratório de Sintese de Farmacos-LASFAR. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Ciências Biomédicas–ICB. Programa de Pós-graduação em Farmacologia e Química Medicinal. Rio de Janeiro, RJ Brasil.
publishDate 2022
dc.date.accessioned.fl_str_mv 2022-12-15T16:03:06Z
dc.date.available.fl_str_mv 2022-12-15T16:03:06Z
dc.date.issued.fl_str_mv 2022
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv SANTOS, Carine et al. Hybrids of Imatinib with Quinoline: Synthesis, Antimyeloproliferative Activity Evaluation, and Molecular Docking. Pharmaceuticals, v.15, 309, p. 1 - 24, Mar. 2022.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/55969
dc.identifier.issn.en_US.fl_str_mv 1999-4923
dc.identifier.doi.none.fl_str_mv 10.3390/ ph15030309
identifier_str_mv SANTOS, Carine et al. Hybrids of Imatinib with Quinoline: Synthesis, Antimyeloproliferative Activity Evaluation, and Molecular Docking. Pharmaceuticals, v.15, 309, p. 1 - 24, Mar. 2022.
1999-4923
10.3390/ ph15030309
url https://www.arca.fiocruz.br/handle/icict/55969
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/55969/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/55969/2/FlorianoJunior_RafaelDantas_etal_IOC_2022.pdf
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repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv repositorio.arca@fiocruz.br
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