New Imatinib Derivatives with Antiproliferative Activity against A549 and K562 Cancer Cells

Detalhes bibliográficos
Autor(a) principal: Oliveira, Andressa
Data de Publicação: 2022
Outros Autores: Moura, Stefany, Pimentel, Luiz, Neto, João, Dantas, Rafael, Silva Jr., Floriano, 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/55947
Resumo: Fundação Oswaldo Cruz. Instituto de Tecnologia em Farmacos-Farmanguinhos. Laboratório de Sintese de Farmacos. Rio de Janeiro, RJ, Brasil / Programa de Pós-graduação em Farmacologia e Química Medicinal do Instituto de Ciências Biomédicas, Centro de Ciências da Saúde. Rio de Janeiro, RJ, Brasil. .
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spelling Oliveira, AndressaMoura, StefanyPimentel, LuizNeto, JoãoDantas, RafaelSilva Jr., FlorianoBastos, MonicaBoechat, Nubia2022-12-15T12:03:23Z2022-12-15T12:03:23Z2022OLIVEIRA, Andressa et al. New Imatinib Derivatives with Antiproliferative Activity against A549 and K562 Cancer Cells. Molecules, v. 27, 750, p. 1-14, Jan. 2022.1420-3049https://www.arca.fiocruz.br/handle/icict/5594710.3390/molecules27030750engMDPINew Imatinib Derivatives with Antiproliferative Activity against A549 and K562 Cancer Cellsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto de Tecnologia em Farmacos-Farmanguinhos. Laboratório de Sintese de Farmacos. Rio de Janeiro, RJ, Brasil / Programa de Pós-graduação em Farmacologia e Química Medicinal do Instituto de Ciências Biomédicas, Centro de Ciências da Saúde. Rio de Janeiro, RJ, Brasil. .Fundação Oswaldo Cruz. Instituto de Tecnologia em Farmacos-Farmanguinhos. Laboratório de Sintese de Farmacos. Rio de Janeiro, RJ, Brasil / Programa de Pós-graduação em Farmacologia e Química Medicinal do Instituto de Ciências Biomédicas, Centro de Ciências da Saúde. Rio de Janeiro, RJ, Brasil. .Fundação Oswaldo Cruz. Instituto de Tecnologia em Farmacos-Farmanguinhos. Laboratório de Sintese de Farmacos. 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.Programa de Pós-graduação em Farmacologia e Química Medicinal do Instituto de Ciências Biomédicas, Centro de Ciências da Saúde. 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. Rio de Janeiro, RJ, Brasil / Programa de Pós-graduação em Farmacologia e Química Medicinal do Instituto de Ciências Biomédicas, Centro de Ciências da Saúde. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Farmacos-Farmanguinhos. Laboratório de Sintese de Farmacos. Rio de Janeiro, RJ, Brasil / Programa de Pós-graduação em Farmacologia e Química Medicinal do Instituto de Ciências Biomédicas, Centro de Ciências da Saúde. Rio de Janeiro, RJ, Brasil.Tyrosine kinase enzymes are among the primary molecular targets for the treatment of some human neoplasms, such as those in lung cancer and chronic myeloid leukemia. Mutations in the enzyme domain can cause resistance and new inhibitors capable of circumventing these mutations are highly desired. The objective of this work was to synthesize and evaluate the antiproliferative ability of ten new analogs that contain isatins and the phenylamino-pyrimidine pyridine (PAPP) skeleton, the main pharmacophore group of imatinib. The 1,2,3-triazole core was used as a spacer in the derivatives through a click chemistry reaction and gave good yields. All the analogs were tested against A549 and K562 cells, lung cancer and chronic myeloid leukemia (CML) cell lines, respectively. In A549 cells, the 3,3-difluorinated compound (3a), the 5-chloro-3,3-difluorinated compound (3c) and the 5-bromo-3,3-difluorinated compound (3d) showed IC50 values of 7.2, 6.4, and 7.3 M, respectively, and were all more potent than imatinib (IC50 of 65.4 M). In K562 cells, the 3,3-difluoro-5-methylated compound (3b) decreased cell viability to 57.5% and, at 10 M, showed an IC50 value of 35.8 M (imatinib, IC50 = 0.08 M). The results suggest that 3a, 3c, and 3d can be used as prototypes for the development of more potent and selective derivatives against lung cancer.Tyrosine kinase inhibitorsImatinibK562A549PAPP and isatininfo: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/55947/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALJoaoNeto_RafaelDantas_etal_IOC_2022.pdfJoaoNeto_RafaelDantas_etal_IOC_2022.pdfapplication/pdf3344706https://www.arca.fiocruz.br/bitstream/icict/55947/2/JoaoNeto_RafaelDantas_etal_IOC_2022.pdf26ef985264886fc5d972b9bbbc0ec12dMD52icict/559472023-09-04 10:54:03.788oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-09-04T13:54:03Repositório Institucional da FIOCRUZ (ARCA) - 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dc.title.en_US.fl_str_mv New Imatinib Derivatives with Antiproliferative Activity against A549 and K562 Cancer Cells
title New Imatinib Derivatives with Antiproliferative Activity against A549 and K562 Cancer Cells
spellingShingle New Imatinib Derivatives with Antiproliferative Activity against A549 and K562 Cancer Cells
Oliveira, Andressa
Tyrosine kinase inhibitors
Imatinib
K562
A549
PAPP and isatin
title_short New Imatinib Derivatives with Antiproliferative Activity against A549 and K562 Cancer Cells
title_full New Imatinib Derivatives with Antiproliferative Activity against A549 and K562 Cancer Cells
title_fullStr New Imatinib Derivatives with Antiproliferative Activity against A549 and K562 Cancer Cells
title_full_unstemmed New Imatinib Derivatives with Antiproliferative Activity against A549 and K562 Cancer Cells
title_sort New Imatinib Derivatives with Antiproliferative Activity against A549 and K562 Cancer Cells
author Oliveira, Andressa
author_facet Oliveira, Andressa
Moura, Stefany
Pimentel, Luiz
Neto, João
Dantas, Rafael
Silva Jr., Floriano
Bastos, Monica
Boechat, Nubia
author_role author
author2 Moura, Stefany
Pimentel, Luiz
Neto, João
Dantas, Rafael
Silva Jr., Floriano
Bastos, Monica
Boechat, Nubia
author2_role author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Oliveira, Andressa
Moura, Stefany
Pimentel, Luiz
Neto, João
Dantas, Rafael
Silva Jr., Floriano
Bastos, Monica
Boechat, Nubia
dc.subject.en.en_US.fl_str_mv Tyrosine kinase inhibitors
Imatinib
K562
A549
PAPP and isatin
topic Tyrosine kinase inhibitors
Imatinib
K562
A549
PAPP and isatin
description Fundação Oswaldo Cruz. Instituto de Tecnologia em Farmacos-Farmanguinhos. Laboratório de Sintese de Farmacos. Rio de Janeiro, RJ, Brasil / Programa de Pós-graduação em Farmacologia e Química Medicinal do Instituto de Ciências Biomédicas, Centro de Ciências da Saúde. Rio de Janeiro, RJ, Brasil. .
publishDate 2022
dc.date.accessioned.fl_str_mv 2022-12-15T12:03:23Z
dc.date.available.fl_str_mv 2022-12-15T12:03:23Z
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 OLIVEIRA, Andressa et al. New Imatinib Derivatives with Antiproliferative Activity against A549 and K562 Cancer Cells. Molecules, v. 27, 750, p. 1-14, Jan. 2022.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/55947
dc.identifier.issn.en_US.fl_str_mv 1420-3049
dc.identifier.doi.none.fl_str_mv 10.3390/molecules27030750
identifier_str_mv OLIVEIRA, Andressa et al. New Imatinib Derivatives with Antiproliferative Activity against A549 and K562 Cancer Cells. Molecules, v. 27, 750, p. 1-14, Jan. 2022.
1420-3049
10.3390/molecules27030750
url https://www.arca.fiocruz.br/handle/icict/55947
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/55947/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/55947/2/JoaoNeto_RafaelDantas_etal_IOC_2022.pdf
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repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
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