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dc.contributor.author
Câmara, Viktor S.
dc.contributor.author
Soares, Ana Julia
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Biscussi, Brunella
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Murray, Ana Paula
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Guedes, Isabella A.
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Dardenne, Laurent E.
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Ruaro, Thaís C.
dc.contributor.author
Zimmer, Aline R.
dc.contributor.author
Ceschi, Marco A.
dc.date.available
2023-09-12T18:56:27Z
dc.date.issued
2021-01
dc.identifier.citation
Câmara, Viktor S.; Soares, Ana Julia; Biscussi, Brunella; Murray, Ana Paula; Guedes, Isabella A.; et al.; Expedient microwave-assisted synthesis of Bis( n )-lophine analogues as selective butyrylcholinesterase inhibitors: Cytotoxicity evaluation and molecular modelling; Sociedade Brasileira de Química; Journal of the Brazilian Chemical Society; 32; 6; 1-2021; 1173-1185
dc.identifier.issn
0103-5053
dc.identifier.uri
http://hdl.handle.net/11336/211297
dc.description.abstract
In the brain of patients with chronic Alzheimer's disease (AD), the butyrylcholinesterase (BuChE) levels rise while the acetylcholinesterase (AChE) levels decrease. Therefore, development of new selective BuChE inhibitors is of vital importance. Here we present a series of bis(n)-lophine analogues, where two lophine derivatives are connected by a methylene chain. The bis(n)-lophine analogues were synthesized through one-pot four component reaction between pyridinecarboxaldehydes, 1,n-alkanediamines, benzil, and ammonium acetate. The reactions were performed in a microwave reactor in one step for symmetrical bis(n)-lophines, and in two steps for unsymmetrical bis(n)-lophines. The compounds are strongly selective to BuChE, since none of them inhibit AChE. All the compounds, except 7a, 7b and 7c, displayed potent inhibitory activity against BuChE at a micromolar and sub-micromolar range (half maximal inhibitory concentration (IC50) 32.25-0.03 μM). The enzyme kinetic and docking studies suggests that the inhibitor act as a dual binding site inhibitor, binding into the bottom of the gorge and in the peripheral anionic site (PAS) of BuChE cavity. Furthermore, in vitro studies showed that compounds 5b and 12b had no cytotoxic effects in kidney Vero, hepatic HepG2 and C6 astroglial cell lines.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Sociedade Brasileira de Química
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
BIS(N)-LOPHINE ANALOGUES
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BUTYRYLCHOLINESTERASE
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CHOLINESTERASE INHIBITOR
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Química Orgánica
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Ciencias Químicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Expedient microwave-assisted synthesis of Bis( n )-lophine analogues as selective butyrylcholinesterase inhibitors: Cytotoxicity evaluation and molecular modelling
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2023-09-12T17:56:34Z
dc.identifier.eissn
1678-4790
dc.journal.volume
32
dc.journal.number
6
dc.journal.pagination
1173-1185
dc.journal.pais
Brasil
dc.journal.ciudad
Sao Paulo
dc.description.fil
Fil: Câmara, Viktor S.. Universidade Federal do Rio Grande do Sul; Brasil
dc.description.fil
Fil: Soares, Ana Julia. Universidade Federal do Rio Grande do Sul; Brasil
dc.description.fil
Fil: Biscussi, Brunella. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina
dc.description.fil
Fil: Murray, Ana Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Química del Sur. Universidad Nacional del Sur. Departamento de Química. Instituto de Química del Sur; Argentina
dc.description.fil
Fil: Guedes, Isabella A.. Laboratório Nacional de Computação Científica; Brasil
dc.description.fil
Fil: Dardenne, Laurent E.. Laboratório Nacional de Computação Científica; Brasil
dc.description.fil
Fil: Ruaro, Thaís C.. Universidade Federal do Rio Grande do Sul; Brasil
dc.description.fil
Fil: Zimmer, Aline R.. Universidade Federal do Rio Grande do Sul; Brasil
dc.description.fil
Fil: Ceschi, Marco A.. Universidade Federal do Rio Grande do Sul; Brasil
dc.journal.title
Journal of the Brazilian Chemical Society
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.scielo.br/j/jbchs/a/VKzV3Kqdvc7zNGnzVMJht8J/
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://s3.sa-east-1.amazonaws.com/static.sites.sbq.org.br/jbcs.sbq.org.br/pdf/2020-0519AR.pdf
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/https://dx.doi.org/10.21577/0103-5053.20210018
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