Identifying new isatin derivatives with GSK-3 inhibition capacity through molecular docking and bioassays

Detalhes bibliográficos
Autor(a) principal: Britto, Karolinni B.
Data de Publicação: 2020
Outros Autores: 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.
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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spelling 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
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution 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
repository.mail.fl_str_mv
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