Exploring Mannosylpurines as Copper Chelators and Cholinesterase Inhibitors with Potential for Alzheimer’s Disease
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2022 |
| 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/10362/150800 |
Resumo: | Funding Information: This research was funded by the EUROPEAN UNION project entitled “Diagnostic and Drug Discovery Initiative for Alzheimer’s Disease” (D3i4AD), FP7-PEOPLE-2013-IAPP. Publisher Copyright: © 2022 by the authors. |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Exploring Mannosylpurines as Copper Chelators and Cholinesterase Inhibitors with Potential for Alzheimer’s DiseaseAlzheimer’s diseasecholinesterase inhibitorscopper chelatorspurine nucleosidesMolecular MedicinePharmaceutical ScienceDrug DiscoverySDG 3 - Good Health and Well-beingFunding Information: This research was funded by the EUROPEAN UNION project entitled “Diagnostic and Drug Discovery Initiative for Alzheimer’s Disease” (D3i4AD), FP7-PEOPLE-2013-IAPP. Publisher Copyright: © 2022 by the authors.Alzheimer’s Disease (AD) is characterized by a progressive cholinergic neurotransmission imbalance, with a decrease of acetylcholinesterase (AChE) activity followed by a significant increase of butyrylcholinesterase (BChE) in the later AD stages. BChE activity is also crucial for the development of Aβ plaques, the main hallmarks of this pathology. Moreover, systemic copper dyshomeostasis alters neurotransmission leading to AD. In the search for structures targeting both events, a set of novel 6-benzamide purine nucleosides was synthesized, differing in glycone configuration and N7/N9 linkage to the purine. Their AChE/BChE inhibitory activity and metal ion chelating properties were evaluated. Selectivity for human BChE inhibition required N9-linked 6-deoxy-α-d-mannosylpurine structure, while all three tested β-d-derivatives appeared as non-selective inhibitors. The N9-linked l-nucleosides were cholinesterase inhibitors except the one embodying either the acetylated sugar or the N-benzyl-protected nucleobase. These findings highlight that sugar-enriched molecular entities can tune bioactivity and selectivity against cholinesterases. In addition, selective copper chelating properties over zinc, aluminum, and iron were found for the benzyl and acetyl-protected 6-deoxy-α-l-mannosyl N9-linked purine nucleosides. Computational studies highlight molecular conformations and the chelating molecular site. The first dual target compounds were disclosed with the perspective of generating drug candidates by improving water solubility.DQ - Departamento de QuímicaRUNSchino, IgnazioCantore, Mariangelade Candia, ModestoAltomare, Cosimo D.Maria, CatarinaBarros, JoãoCachatra, VascoCalado, PatríciaShimizu, KarinaFreitas, Adilson A.Oliveira, Maria C.Ferreira, Maria J.Lopes, José N. C.Colabufo, Nicola A.Rauter, Amélia P.2023-03-17T22:31:13Z2022-12-302022-12-30T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article20application/pdfhttp://hdl.handle.net/10362/150800eng1424-8247PURE: 56207033https://doi.org/10.3390/ph16010054info: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:RCAAP2024-03-11T05:33:14Zoai:run.unl.pt:10362/150800Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:54:19.634241Repositório 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 |
Exploring Mannosylpurines as Copper Chelators and Cholinesterase Inhibitors with Potential for Alzheimer’s Disease |
| title |
Exploring Mannosylpurines as Copper Chelators and Cholinesterase Inhibitors with Potential for Alzheimer’s Disease |
| spellingShingle |
Exploring Mannosylpurines as Copper Chelators and Cholinesterase Inhibitors with Potential for Alzheimer’s Disease Schino, Ignazio Alzheimer’s disease cholinesterase inhibitors copper chelators purine nucleosides Molecular Medicine Pharmaceutical Science Drug Discovery SDG 3 - Good Health and Well-being |
| title_short |
Exploring Mannosylpurines as Copper Chelators and Cholinesterase Inhibitors with Potential for Alzheimer’s Disease |
| title_full |
Exploring Mannosylpurines as Copper Chelators and Cholinesterase Inhibitors with Potential for Alzheimer’s Disease |
| title_fullStr |
Exploring Mannosylpurines as Copper Chelators and Cholinesterase Inhibitors with Potential for Alzheimer’s Disease |
| title_full_unstemmed |
Exploring Mannosylpurines as Copper Chelators and Cholinesterase Inhibitors with Potential for Alzheimer’s Disease |
| title_sort |
Exploring Mannosylpurines as Copper Chelators and Cholinesterase Inhibitors with Potential for Alzheimer’s Disease |
| author |
Schino, Ignazio |
| author_facet |
Schino, Ignazio Cantore, Mariangela de Candia, Modesto Altomare, Cosimo D. Maria, Catarina Barros, João Cachatra, Vasco Calado, Patrícia Shimizu, Karina Freitas, Adilson A. Oliveira, Maria C. Ferreira, Maria J. Lopes, José N. C. Colabufo, Nicola A. Rauter, Amélia P. |
| author_role |
author |
| author2 |
Cantore, Mariangela de Candia, Modesto Altomare, Cosimo D. Maria, Catarina Barros, João Cachatra, Vasco Calado, Patrícia Shimizu, Karina Freitas, Adilson A. Oliveira, Maria C. Ferreira, Maria J. Lopes, José N. C. Colabufo, Nicola A. Rauter, Amélia P. |
| author2_role |
author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
DQ - Departamento de Química RUN |
| dc.contributor.author.fl_str_mv |
Schino, Ignazio Cantore, Mariangela de Candia, Modesto Altomare, Cosimo D. Maria, Catarina Barros, João Cachatra, Vasco Calado, Patrícia Shimizu, Karina Freitas, Adilson A. Oliveira, Maria C. Ferreira, Maria J. Lopes, José N. C. Colabufo, Nicola A. Rauter, Amélia P. |
| dc.subject.por.fl_str_mv |
Alzheimer’s disease cholinesterase inhibitors copper chelators purine nucleosides Molecular Medicine Pharmaceutical Science Drug Discovery SDG 3 - Good Health and Well-being |
| topic |
Alzheimer’s disease cholinesterase inhibitors copper chelators purine nucleosides Molecular Medicine Pharmaceutical Science Drug Discovery SDG 3 - Good Health and Well-being |
| description |
Funding Information: This research was funded by the EUROPEAN UNION project entitled “Diagnostic and Drug Discovery Initiative for Alzheimer’s Disease” (D3i4AD), FP7-PEOPLE-2013-IAPP. Publisher Copyright: © 2022 by the authors. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022-12-30 2022-12-30T00:00:00Z 2023-03-17T22:31:13Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/150800 |
| url |
http://hdl.handle.net/10362/150800 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
1424-8247 PURE: 56207033 https://doi.org/10.3390/ph16010054 |
| dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
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20 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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