Identifying new isatin derivatives with GSK-3 inhibition capacity through molecular docking and bioassays
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/65586 |
Resumo: | The semi-synthesis of 11 isatin derivatives was achieved through bimolecular nucleophilic substitution and click chemistry. Seven new compounds were obtained. All chemical structures were determined by infrared spectroscopy (IR), nuclear magnetic resonance spectrometry (NMR) and high-resolution mass spectrometry (HRMS) data. These derivatives were evaluated for their anti-GSK-3 activity and all isatin derivatives (N-alkyl and 1,2,3-triazolic) exhibited strong inhibitory activity, with 2b and 4h exhibiting remarkable potency. In addition, docking studies were performed with 2b and 2e models to unravel the molecular mechanism underlying the polar interactions on the GSK-3 ATP-binding site. |
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Identifying new isatin derivatives with GSK-3 inhibition capacity through molecular docking and bioassaysisatin derivativesGSK-3ßmolecular dockingGSK-3βScience & TechnologyThe semi-synthesis of 11 isatin derivatives was achieved through bimolecular nucleophilic substitution and click chemistry. Seven new compounds were obtained. All chemical structures were determined by infrared spectroscopy (IR), nuclear magnetic resonance spectrometry (NMR) and high-resolution mass spectrometry (HRMS) data. These derivatives were evaluated for their anti-GSK-3 activity and all isatin derivatives (N-alkyl and 1,2,3-triazolic) exhibited strong inhibitory activity, with 2b and 4h exhibiting remarkable potency. In addition, docking studies were performed with 2b and 2e models to unravel the molecular mechanism underlying the polar interactions on the GSK-3 ATP-binding site.This study was funded by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brasil (CAPES), Finance Code 001, by the National Council of Scientific and Technological Development (CNPq) and Foundation of Support to Research and Innovation of Espírito Santo (FAPES PPE-Agro No. 76418880/16). We also would like to acknowledge INCTBioNat (CNPq 465637/2014-0) for additional support and NCQP-UFES, as well as the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2019 unit and BioTecNorte operation (NORTE-01-0145-FEDER-000004) funded by the European Regional Development Fund under the scope of Norte2020, Programa Operacional Regional do Norte. L. R. R. also acknowledges her sabbatical leave fellowship (SFRH/BSAB/142991/2018) funded by FCT. D. F. is recipient of a doctoral fellowship (call NORTE-69-2015-15) funded by the European Social Fund under the scope of Norte2020, Programa Operacional Regional do Norte.info:eu-repo/semantics/publishedVersionSociedade Brasileira de QuímicaUniversidade do MinhoBritto, Karolinni B.Francisco, Carla S.Ferreira, DéboraBorges, Bárbara J. P.Conti, RaphaelProfeti, DemetriusRodrigues, L. R.Lacerda Jr. , ValdemarMorais, Pedro A. B.Borges, Warley S.2020-032020-03-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/65586engBritto, Karolinni B.; Francisco, Carla S.; Ferreira, Débora; Borges, Bárbara J. P.; Conti, Raphael; Profeti, Demetrius; Rodrigues, Lígia R.; Lacerda Jr. , Valdemar; Morais, Pedro A. B.; Borges, Warley S., Identifying new isatin derivatives with GSK-3 inhibition capacity through molecular docking and bioassays. Journal of the Brazilian Chemical Society, 31(3), 476-487, 20200103-505310.21577/0103-5053.20190206http://jbcs.sbq.org.brinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:51:57Zoai:repositorium.sdum.uminho.pt:1822/65586Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:50:59.378202Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Identifying new isatin derivatives with GSK-3 inhibition capacity through molecular docking and bioassays |
title |
Identifying new isatin derivatives with GSK-3 inhibition capacity through molecular docking and bioassays |
spellingShingle |
Identifying new isatin derivatives with GSK-3 inhibition capacity through molecular docking and bioassays Britto, Karolinni B. isatin derivatives GSK-3ß molecular docking GSK-3β Science & Technology |
title_short |
Identifying new isatin derivatives with GSK-3 inhibition capacity through molecular docking and bioassays |
title_full |
Identifying new isatin derivatives with GSK-3 inhibition capacity through molecular docking and bioassays |
title_fullStr |
Identifying new isatin derivatives with GSK-3 inhibition capacity through molecular docking and bioassays |
title_full_unstemmed |
Identifying new isatin derivatives with GSK-3 inhibition capacity through molecular docking and bioassays |
title_sort |
Identifying new isatin derivatives with GSK-3 inhibition capacity through molecular docking and bioassays |
author |
Britto, Karolinni B. |
author_facet |
Britto, Karolinni B. Francisco, Carla S. Ferreira, Débora Borges, Bárbara J. P. Conti, Raphael Profeti, Demetrius Rodrigues, L. R. Lacerda Jr. , Valdemar Morais, Pedro A. B. Borges, Warley S. |
author_role |
author |
author2 |
Francisco, Carla S. Ferreira, Débora Borges, Bárbara J. P. Conti, Raphael Profeti, Demetrius Rodrigues, L. R. Lacerda Jr. , Valdemar Morais, Pedro A. B. Borges, Warley S. |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Britto, Karolinni B. Francisco, Carla S. Ferreira, Débora Borges, Bárbara J. P. Conti, Raphael Profeti, Demetrius Rodrigues, L. R. Lacerda Jr. , Valdemar Morais, Pedro A. B. Borges, Warley S. |
dc.subject.por.fl_str_mv |
isatin derivatives GSK-3ß molecular docking GSK-3β Science & Technology |
topic |
isatin derivatives GSK-3ß molecular docking GSK-3β Science & Technology |
description |
The semi-synthesis of 11 isatin derivatives was achieved through bimolecular nucleophilic substitution and click chemistry. Seven new compounds were obtained. All chemical structures were determined by infrared spectroscopy (IR), nuclear magnetic resonance spectrometry (NMR) and high-resolution mass spectrometry (HRMS) data. These derivatives were evaluated for their anti-GSK-3 activity and all isatin derivatives (N-alkyl and 1,2,3-triazolic) exhibited strong inhibitory activity, with 2b and 4h exhibiting remarkable potency. In addition, docking studies were performed with 2b and 2e models to unravel the molecular mechanism underlying the polar interactions on the GSK-3 ATP-binding site. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-03 2020-03-01T00:00:00Z |
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.uri.fl_str_mv |
http://hdl.handle.net/1822/65586 |
url |
http://hdl.handle.net/1822/65586 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Britto, Karolinni B.; Francisco, Carla S.; Ferreira, Débora; Borges, Bárbara J. P.; Conti, Raphael; Profeti, Demetrius; Rodrigues, Lígia R.; Lacerda Jr. , Valdemar; Morais, Pedro A. B.; Borges, Warley S., Identifying new isatin derivatives with GSK-3 inhibition capacity through molecular docking and bioassays. Journal of the Brazilian Chemical Society, 31(3), 476-487, 2020 0103-5053 10.21577/0103-5053.20190206 http://jbcs.sbq.org.br |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Sociedade Brasileira de Química |
publisher.none.fl_str_mv |
Sociedade Brasileira de Química |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799133096256208896 |