Acetylcholinesterase Choline-Based Ionic Liquid Inhibitors: In Vitro and in Silico Molecular Docking Studies
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2018 |
| 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/10362/104680 |
Resumo: | COMPETE Programme: SAICTPAC/0019/2015 IF/00780/2015 Project no. 022161 |
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Acetylcholinesterase Choline-Based Ionic Liquid Inhibitors: In Vitro and in Silico Molecular Docking StudiesChemistry(all)Chemical Engineering(all)SDG 3 - Good Health and Well-beingCOMPETE Programme: SAICTPAC/0019/2015 IF/00780/2015 Project no. 022161Monocationic and dicationic cholinium ionic liquids (ILs) were synthesized and evaluated as acetylcholinesterase (AChE) inhibitors with in vitro and in silico models, and their cytotoxicity was assessed using human cell lines from skin (CRL-1502) and colon cancer (CaCo-2). The ILs with a longer alkyl chain were stronger AChE inhibitors, the dicationic ILs (DILs) being more active than the monocationic ILs. The best result was obtained for [N1,1,12,2(OH)]2Br2 at a concentration of 0.18 μM by reducing half enzyme activity without affecting the viability of tested cell lines. A saturation-transfer difference NMR (STD-NMR) binding study was carried out, demonstrating that [N1,1,12,2(OH)]2Br2 binds to AChE. STD-NMR competition binding experiments, using galanthamine as a reference ligand, clearly highlight that the IL displaces galanthamine in the AChE binding site pinpointing [N1,1,12,2(OH)]2Br2 inside the deep gorge of AChE. In order to obtain a three-dimensional (3D) view of the molecular recognition process, in silico molecular docking studies on the active site of AChE were carried out. The proposed 3D model of the AChE/DIL complex is in agreement with the STD-derived epitope mapping, which explains the competition with galanthamine and unveils key interactions in both peripheral and catalytic sites of AChE. These interactions seem essential to govern the recognition of DILs by the AChE enzyme. Our study provides a structural and functional platform that can be used for the rational design of choline-based ILs as potent AChE inhibitors.DQ - Departamento de QuímicaUCIBIO - Applied Molecular Biosciences UnitRUNSiopa, FilipaFrade, Raquel F. M.Diniz, AnaAndrade, Joana M.Nicolai, MarisaMeirinhos, AnaLucas, Susana D.Marcelo, FilipaAfonso, Carlos A. M.Rijo, Patrícia2020-09-24T22:35:47Z2018-12-122018-12-12T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article10application/pdfhttp://hdl.handle.net/10362/104680eng2470-1343PURE: 12262649https://doi.org/10.1021/acsomega.8b02347info: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:RCAAP2024-05-22T17:47:48Zoai:run.unl.pt:10362/104680Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-05-22T17:47:48Repositório 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 |
Acetylcholinesterase Choline-Based Ionic Liquid Inhibitors: In Vitro and in Silico Molecular Docking Studies |
| title |
Acetylcholinesterase Choline-Based Ionic Liquid Inhibitors: In Vitro and in Silico Molecular Docking Studies |
| spellingShingle |
Acetylcholinesterase Choline-Based Ionic Liquid Inhibitors: In Vitro and in Silico Molecular Docking Studies Siopa, Filipa Chemistry(all) Chemical Engineering(all) SDG 3 - Good Health and Well-being |
| title_short |
Acetylcholinesterase Choline-Based Ionic Liquid Inhibitors: In Vitro and in Silico Molecular Docking Studies |
| title_full |
Acetylcholinesterase Choline-Based Ionic Liquid Inhibitors: In Vitro and in Silico Molecular Docking Studies |
| title_fullStr |
Acetylcholinesterase Choline-Based Ionic Liquid Inhibitors: In Vitro and in Silico Molecular Docking Studies |
| title_full_unstemmed |
Acetylcholinesterase Choline-Based Ionic Liquid Inhibitors: In Vitro and in Silico Molecular Docking Studies |
| title_sort |
Acetylcholinesterase Choline-Based Ionic Liquid Inhibitors: In Vitro and in Silico Molecular Docking Studies |
| author |
Siopa, Filipa |
| author_facet |
Siopa, Filipa Frade, Raquel F. M. Diniz, Ana Andrade, Joana M. Nicolai, Marisa Meirinhos, Ana Lucas, Susana D. Marcelo, Filipa Afonso, Carlos A. M. Rijo, Patrícia |
| author_role |
author |
| author2 |
Frade, Raquel F. M. Diniz, Ana Andrade, Joana M. Nicolai, Marisa Meirinhos, Ana Lucas, Susana D. Marcelo, Filipa Afonso, Carlos A. M. Rijo, Patrícia |
| author2_role |
author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
DQ - Departamento de Química UCIBIO - Applied Molecular Biosciences Unit RUN |
| dc.contributor.author.fl_str_mv |
Siopa, Filipa Frade, Raquel F. M. Diniz, Ana Andrade, Joana M. Nicolai, Marisa Meirinhos, Ana Lucas, Susana D. Marcelo, Filipa Afonso, Carlos A. M. Rijo, Patrícia |
| dc.subject.por.fl_str_mv |
Chemistry(all) Chemical Engineering(all) SDG 3 - Good Health and Well-being |
| topic |
Chemistry(all) Chemical Engineering(all) SDG 3 - Good Health and Well-being |
| description |
COMPETE Programme: SAICTPAC/0019/2015 IF/00780/2015 Project no. 022161 |
| publishDate |
2018 |
| dc.date.none.fl_str_mv |
2018-12-12 2018-12-12T00:00:00Z 2020-09-24T22:35:47Z |
| 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/10362/104680 |
| url |
http://hdl.handle.net/10362/104680 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
2470-1343 PURE: 12262649 https://doi.org/10.1021/acsomega.8b02347 |
| dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
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10 application/pdf |
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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 |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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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 |
| repository.mail.fl_str_mv |
mluisa.alvim@gmail.com |
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1817545760310296576 |