Discovery of thiazolo [5,4-c] isoquinoline based compounds as acetylcholinesterase inhibitors through computational target prediction, molecular docking and bioassay
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2023 |
| 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/10362/154770 |
Resumo: | We thank Nathalie Reichmann and Leendert Hamoen (University of Amsterdam) for critical reading of the manuscript, Ana Velic (Proteome Center Tübingen) for help with proteome analysis and Mike VanNieuwenhze (Indiana University) for the generous gift of HADA. This study was funded by the European Research Council through grant ERC‐2017‐CoG‐771709 (to MGP), by national funds through FCT– Fundação para a Ciência e a Tecnologia, PTDC/BIA‐MIC/6982/2020 (to HV); PTDC/BIA‐PLA/3432/2012 (to SRF); by the Swiss National National Foundation through P300P3_155346 (to AJ); by the European Molecular Biology Organization through award ALTF 673‐2018 (to SS). Figure 6D and Appendix Fig S7 were created with Biorender.com . |
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Discovery of thiazolo [5,4-c] isoquinoline based compounds as acetylcholinesterase inhibitors through computational target prediction, molecular docking and bioassayWe thank Nathalie Reichmann and Leendert Hamoen (University of Amsterdam) for critical reading of the manuscript, Ana Velic (Proteome Center Tübingen) for help with proteome analysis and Mike VanNieuwenhze (Indiana University) for the generous gift of HADA. This study was funded by the European Research Council through grant ERC‐2017‐CoG‐771709 (to MGP), by national funds through FCT– Fundação para a Ciência e a Tecnologia, PTDC/BIA‐MIC/6982/2020 (to HV); PTDC/BIA‐PLA/3432/2012 (to SRF); by the Swiss National National Foundation through P300P3_155346 (to AJ); by the European Molecular Biology Organization through award ALTF 673‐2018 (to SS). Figure 6D and Appendix Fig S7 were created with Biorender.com .A computer-aided drug design (CADD) approach was developed for a focused chemical library comprising a series of sixteen thiazolo[5,4-c]isoquinoline derivatives. Little is known about this group of heteroaromatic compounds, both from the point of view of their synthesis and their biological properties. First, our CADD approach included target prediction by Mondrian conformal prediction with the ChEMBL database. The acetylcholinesterase (AChE) was identified as having a high probability of thiazolo[5,4-c]isoquinolines being active against it. Secondly, the molecular docking predictions revealed four promising thiazoloisoquinolines (2, 7, 13 and 14) according to their prominent ligand-protein energy scores and relevant binding affinities with the AChE pocket residues. The subsequent in vitro evaluation of promising hits and related ones revealed a set of novel AChE inhibitors. Therefore, the findings reported herein may provide a new strategy for discovering novel AChE inhibitors.LAQV@REQUIMTEDQ - Departamento de QuímicaRUNCosta, Letícia D.Silva, Carlos F. M.Pinto, Diana C. G. A.Silva, Artur M. S.Pereira, FlorbelaFaustino, Maria Amparo F.Tomé, Augusto C.2023-07-03T22:16:58Z2023-11-052023-11-05T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article8application/pdfhttp://hdl.handle.net/10362/154770eng0022-2860PURE: 65193006https://doi.org/10.1016/j.molstruc.2023.136088info: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:RCAAP2024-05-22T18:12:34Zoai:run.unl.pt:10362/154770Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-05-22T18:12:34Repositório 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 |
Discovery of thiazolo [5,4-c] isoquinoline based compounds as acetylcholinesterase inhibitors through computational target prediction, molecular docking and bioassay |
| title |
Discovery of thiazolo [5,4-c] isoquinoline based compounds as acetylcholinesterase inhibitors through computational target prediction, molecular docking and bioassay |
| spellingShingle |
Discovery of thiazolo [5,4-c] isoquinoline based compounds as acetylcholinesterase inhibitors through computational target prediction, molecular docking and bioassay Costa, Letícia D. |
| title_short |
Discovery of thiazolo [5,4-c] isoquinoline based compounds as acetylcholinesterase inhibitors through computational target prediction, molecular docking and bioassay |
| title_full |
Discovery of thiazolo [5,4-c] isoquinoline based compounds as acetylcholinesterase inhibitors through computational target prediction, molecular docking and bioassay |
| title_fullStr |
Discovery of thiazolo [5,4-c] isoquinoline based compounds as acetylcholinesterase inhibitors through computational target prediction, molecular docking and bioassay |
| title_full_unstemmed |
Discovery of thiazolo [5,4-c] isoquinoline based compounds as acetylcholinesterase inhibitors through computational target prediction, molecular docking and bioassay |
| title_sort |
Discovery of thiazolo [5,4-c] isoquinoline based compounds as acetylcholinesterase inhibitors through computational target prediction, molecular docking and bioassay |
| author |
Costa, Letícia D. |
| author_facet |
Costa, Letícia D. Silva, Carlos F. M. Pinto, Diana C. G. A. Silva, Artur M. S. Pereira, Florbela Faustino, Maria Amparo F. Tomé, Augusto C. |
| author_role |
author |
| author2 |
Silva, Carlos F. M. Pinto, Diana C. G. A. Silva, Artur M. S. Pereira, Florbela Faustino, Maria Amparo F. Tomé, Augusto C. |
| author2_role |
author author author author author author |
| dc.contributor.none.fl_str_mv |
LAQV@REQUIMTE DQ - Departamento de Química RUN |
| dc.contributor.author.fl_str_mv |
Costa, Letícia D. Silva, Carlos F. M. Pinto, Diana C. G. A. Silva, Artur M. S. Pereira, Florbela Faustino, Maria Amparo F. Tomé, Augusto C. |
| description |
We thank Nathalie Reichmann and Leendert Hamoen (University of Amsterdam) for critical reading of the manuscript, Ana Velic (Proteome Center Tübingen) for help with proteome analysis and Mike VanNieuwenhze (Indiana University) for the generous gift of HADA. This study was funded by the European Research Council through grant ERC‐2017‐CoG‐771709 (to MGP), by national funds through FCT– Fundação para a Ciência e a Tecnologia, PTDC/BIA‐MIC/6982/2020 (to HV); PTDC/BIA‐PLA/3432/2012 (to SRF); by the Swiss National National Foundation through P300P3_155346 (to AJ); by the European Molecular Biology Organization through award ALTF 673‐2018 (to SS). Figure 6D and Appendix Fig S7 were created with Biorender.com . |
| publishDate |
2023 |
| dc.date.none.fl_str_mv |
2023-07-03T22:16:58Z 2023-11-05 2023-11-05T00:00:00Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
| format |
article |
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publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/154770 |
| url |
http://hdl.handle.net/10362/154770 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
0022-2860 PURE: 65193006 https://doi.org/10.1016/j.molstruc.2023.136088 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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8 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 |
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mluisa.alvim@gmail.com |
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1817545941743304704 |