Ugi Reaction Synthesis of Oxindole-Lactam Hybrids as Selective Butyrylcholinesterase Inhibitors
Autor(a) principal: | |
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Data de Publicação: | 2021 |
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/10316/107441 https://doi.org/10.1021/acsmedchemlett.1c00344 |
Resumo: | Molecular hybridization is a valuable approach in drug discovery. Combining it with multicomponent reactions is highly desirable, since structurally diverse libraries can be attained efficiently in an eco-friendly manner. In this work, isatin is used as the key building block for the Ugi 4-center 3-component reaction synthesis of oxindole-lactam hybrids, under catalyst-free conditions. The resulting oxindole-β-lactam and oxindole-γ-lactam hybrids were evaluated for their potential to inhibit relevant central nervous system targets, namely cholinesterases and monoamine oxidases. Druglikeness evaluation was also performed, and compounds 4eca and 5dab exhibited great potential as selective butyrylcholinesterase inhibitors, at the low micromolar range, with an interesting predictive pharmacokinetic profile. Our findings herein reported suggest oxindole-lactam hybrids as new potential agents for the treatment of Alzheimer's disease. |
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Ugi Reaction Synthesis of Oxindole-Lactam Hybrids as Selective Butyrylcholinesterase InhibitorsMolecular hybridization is a valuable approach in drug discovery. Combining it with multicomponent reactions is highly desirable, since structurally diverse libraries can be attained efficiently in an eco-friendly manner. In this work, isatin is used as the key building block for the Ugi 4-center 3-component reaction synthesis of oxindole-lactam hybrids, under catalyst-free conditions. The resulting oxindole-β-lactam and oxindole-γ-lactam hybrids were evaluated for their potential to inhibit relevant central nervous system targets, namely cholinesterases and monoamine oxidases. Druglikeness evaluation was also performed, and compounds 4eca and 5dab exhibited great potential as selective butyrylcholinesterase inhibitors, at the low micromolar range, with an interesting predictive pharmacokinetic profile. Our findings herein reported suggest oxindole-lactam hybrids as new potential agents for the treatment of Alzheimer's disease.ACS American Chemical Society2021-11-11info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/107441http://hdl.handle.net/10316/107441https://doi.org/10.1021/acsmedchemlett.1c00344eng1948-5875Brandão, PedroLópez, ÓscarLeitzbach, LuisaStark, HolgerFernández-Bolaños, José G.Burke, Anthony J.Pineiro, Martainfo: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:RCAAP2023-07-12T09:27:46Zoai:estudogeral.uc.pt:10316/107441Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:23:47.895549Repositório 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 |
Ugi Reaction Synthesis of Oxindole-Lactam Hybrids as Selective Butyrylcholinesterase Inhibitors |
title |
Ugi Reaction Synthesis of Oxindole-Lactam Hybrids as Selective Butyrylcholinesterase Inhibitors |
spellingShingle |
Ugi Reaction Synthesis of Oxindole-Lactam Hybrids as Selective Butyrylcholinesterase Inhibitors Brandão, Pedro |
title_short |
Ugi Reaction Synthesis of Oxindole-Lactam Hybrids as Selective Butyrylcholinesterase Inhibitors |
title_full |
Ugi Reaction Synthesis of Oxindole-Lactam Hybrids as Selective Butyrylcholinesterase Inhibitors |
title_fullStr |
Ugi Reaction Synthesis of Oxindole-Lactam Hybrids as Selective Butyrylcholinesterase Inhibitors |
title_full_unstemmed |
Ugi Reaction Synthesis of Oxindole-Lactam Hybrids as Selective Butyrylcholinesterase Inhibitors |
title_sort |
Ugi Reaction Synthesis of Oxindole-Lactam Hybrids as Selective Butyrylcholinesterase Inhibitors |
author |
Brandão, Pedro |
author_facet |
Brandão, Pedro López, Óscar Leitzbach, Luisa Stark, Holger Fernández-Bolaños, José G. Burke, Anthony J. Pineiro, Marta |
author_role |
author |
author2 |
López, Óscar Leitzbach, Luisa Stark, Holger Fernández-Bolaños, José G. Burke, Anthony J. Pineiro, Marta |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Brandão, Pedro López, Óscar Leitzbach, Luisa Stark, Holger Fernández-Bolaños, José G. Burke, Anthony J. Pineiro, Marta |
description |
Molecular hybridization is a valuable approach in drug discovery. Combining it with multicomponent reactions is highly desirable, since structurally diverse libraries can be attained efficiently in an eco-friendly manner. In this work, isatin is used as the key building block for the Ugi 4-center 3-component reaction synthesis of oxindole-lactam hybrids, under catalyst-free conditions. The resulting oxindole-β-lactam and oxindole-γ-lactam hybrids were evaluated for their potential to inhibit relevant central nervous system targets, namely cholinesterases and monoamine oxidases. Druglikeness evaluation was also performed, and compounds 4eca and 5dab exhibited great potential as selective butyrylcholinesterase inhibitors, at the low micromolar range, with an interesting predictive pharmacokinetic profile. Our findings herein reported suggest oxindole-lactam hybrids as new potential agents for the treatment of Alzheimer's disease. |
publishDate |
2021 |
dc.date.none.fl_str_mv |
2021-11-11 |
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/10316/107441 http://hdl.handle.net/10316/107441 https://doi.org/10.1021/acsmedchemlett.1c00344 |
url |
http://hdl.handle.net/10316/107441 https://doi.org/10.1021/acsmedchemlett.1c00344 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1948-5875 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
ACS American Chemical Society |
publisher.none.fl_str_mv |
ACS American Chemical Society |
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 |
instacron_str |
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) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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