Ugi Adducts of Isatin as Promising Antiproliferative Agents with Druglike Properties
Autor(a) principal: | |
---|---|
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/10316/107506 https://doi.org/10.1002/ajoc.202100684 |
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 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 inhibition, 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. |
id |
RCAP_e54a26440078f835e53ebe7e82654af4 |
---|---|
oai_identifier_str |
oai:estudogeral.uc.pt:10316/107506 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
spelling |
Ugi Adducts of Isatin as Promising Antiproliferative Agents with Druglike Propertiesisatinmulticomponent reactionsUgi reactionAlzheimer’s diseaseoxindole-lactam hybridsMolecular 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 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 inhibition, 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.P. Brandão acknowledges FCT for the PhD grant PD/BD/128490/2017–CATSUS FCT-PhD Program. Coimbra Chemistry Centre (CQC) is supported by the Portuguese Agency for Scientific Research, “Fundação para a Ciência e a Tecnologia” (FCT) through project UIDB/00313/2020 and UIDP/00313/2020, co-funded by COMPETE2020-UE. We also acknowledge the UC-NMR facility for obtaining the NMR data (www.nmrccc.uc.pt).This work was also financed by the FEDER Funds through the Operational Competitiveness Factors Program – COMPETE and by National Funds through FCT - Foundation for Science and Technology within the scope of the project UIDB/50006/2020. Ó. López would also like to thank the Dirección General de Investigación of Spain (CTQ2016-78703-P), Junta de Andalucía (FQM134) and FEDER (501100008530) for financial support. Partial support from the EU COST Actions CA15135 (to HS and AJB), CA18133 (to HS) and CA18240 (to HS) is also acknowledged.Wiley Online Library2021info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/107506http://hdl.handle.net/10316/107506https://doi.org/10.1002/ajoc.202100684eng2193-58072193-5815Brandão, PedroPuerta, AdriánPadrón, José M.Kuznetsov, Maxim L.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:RCAAP2023-07-18T08:04:35Zoai:estudogeral.uc.pt:10316/107506Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:23:50.714417Repositório 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 Adducts of Isatin as Promising Antiproliferative Agents with Druglike Properties |
title |
Ugi Adducts of Isatin as Promising Antiproliferative Agents with Druglike Properties |
spellingShingle |
Ugi Adducts of Isatin as Promising Antiproliferative Agents with Druglike Properties Brandão, Pedro isatin multicomponent reactions Ugi reaction Alzheimer’s disease oxindole-lactam hybrids |
title_short |
Ugi Adducts of Isatin as Promising Antiproliferative Agents with Druglike Properties |
title_full |
Ugi Adducts of Isatin as Promising Antiproliferative Agents with Druglike Properties |
title_fullStr |
Ugi Adducts of Isatin as Promising Antiproliferative Agents with Druglike Properties |
title_full_unstemmed |
Ugi Adducts of Isatin as Promising Antiproliferative Agents with Druglike Properties |
title_sort |
Ugi Adducts of Isatin as Promising Antiproliferative Agents with Druglike Properties |
author |
Brandão, Pedro |
author_facet |
Brandão, Pedro Puerta, Adrián Padrón, José M. Kuznetsov, Maxim L. Burke, Anthony J. Pineiro, Marta |
author_role |
author |
author2 |
Puerta, Adrián Padrón, José M. Kuznetsov, Maxim L. Burke, Anthony J. Pineiro, Marta |
author2_role |
author author author author author |
dc.contributor.author.fl_str_mv |
Brandão, Pedro Puerta, Adrián Padrón, José M. Kuznetsov, Maxim L. Burke, Anthony J. Pineiro, Marta |
dc.subject.por.fl_str_mv |
isatin multicomponent reactions Ugi reaction Alzheimer’s disease oxindole-lactam hybrids |
topic |
isatin multicomponent reactions Ugi reaction Alzheimer’s disease oxindole-lactam hybrids |
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 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 inhibition, 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 |
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/10316/107506 http://hdl.handle.net/10316/107506 https://doi.org/10.1002/ajoc.202100684 |
url |
http://hdl.handle.net/10316/107506 https://doi.org/10.1002/ajoc.202100684 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2193-5807 2193-5815 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Wiley Online Library |
publisher.none.fl_str_mv |
Wiley Online Library |
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 |
|
_version_ |
1799134124515000320 |