Design, synthesis and biological evaluation of 1,3-dihydroxyxanthone derivatives: Effective agents against acetylcholinesterase

Autores
Menéndez, Cintia Anabella; Biscussi, Brunella; Accordino, Sebastian Roberto; Murray, Ana Paula; Gerbino, Darío César; Appignanesi, Gustavo Adrian
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The present work concerns the rational design and development of new inhibitors of acetylcholinesterase (AChE) based on the privileged xanthone scaffold. In order to understand and rationalize the mode of action of these target structures a theoretical study was initially conducted. From the results of rational design, a new variety of amphiphilic xanthone derivatives were synthesized, structurally characterized and evaluated as potential anti-Alzheimer agents. The results showed that most of the synthesized compounds exhibited high AChE inhibitory activity at the micromolar range (IC50, 0.46–12.09 μM). The synthetic xanthone 11 showed the best inhibitory effect on AChE and a molecular modeling study revealed that 11 targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Therefore, this compound could be considered as a potential lead compound towards new drugs for the treatment of Alzheimer’s disease.
Fil: Menéndez, Cintia Anabella. 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
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
Fil: Accordino, Sebastian Roberto. 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
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
Fil: Gerbino, Darío César. 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
Fil: Appignanesi, Gustavo Adrian. 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
Materia
XANTHONES
ACHE
MOLECULAR DYNAMICS
MOLECULAR DOCKING
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/42719
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/42719
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Design, synthesis and biological evaluation of 1,3-dihydroxyxanthone derivatives: Effective agents against acetylcholinesteraseMenéndez, Cintia AnabellaBiscussi, BrunellaAccordino, Sebastian RobertoMurray, Ana PaulaGerbino, Darío CésarAppignanesi, Gustavo AdrianXANTHONESACHEMOLECULAR DYNAMICSMOLECULAR DOCKINGhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1The present work concerns the rational design and development of new inhibitors of acetylcholinesterase (AChE) based on the privileged xanthone scaffold. In order to understand and rationalize the mode of action of these target structures a theoretical study was initially conducted. From the results of rational design, a new variety of amphiphilic xanthone derivatives were synthesized, structurally characterized and evaluated as potential anti-Alzheimer agents. The results showed that most of the synthesized compounds exhibited high AChE inhibitory activity at the micromolar range (IC50, 0.46–12.09 μM). The synthetic xanthone 11 showed the best inhibitory effect on AChE and a molecular modeling study revealed that 11 targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Therefore, this compound could be considered as a potential lead compound towards new drugs for the treatment of Alzheimer’s disease.Fil: Menéndez, Cintia Anabella. 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; ArgentinaFil: 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; ArgentinaFil: Accordino, Sebastian Roberto. 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; ArgentinaFil: 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; ArgentinaFil: Gerbino, Darío César. 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; ArgentinaFil: Appignanesi, Gustavo Adrian. 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; ArgentinaAcademic Press Inc Elsevier Science2017-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/42719Menéndez, Cintia Anabella; Biscussi, Brunella; Accordino, Sebastian Roberto; Murray, Ana Paula; Gerbino, Darío César; et al.; Design, synthesis and biological evaluation of 1,3-dihydroxyxanthone derivatives: Effective agents against acetylcholinesterase; Academic Press Inc Elsevier Science; Bioorganic Chemistry; 75; 9-2017; 201-2090045-2068CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0045206817305527info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bioorg.2017.09.012info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:35:20Zoai:ri.conicet.gov.ar:11336/42719instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:35:20.591CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Design, synthesis and biological evaluation of 1,3-dihydroxyxanthone derivatives: Effective agents against acetylcholinesterase
title Design, synthesis and biological evaluation of 1,3-dihydroxyxanthone derivatives: Effective agents against acetylcholinesterase
spellingShingle Design, synthesis and biological evaluation of 1,3-dihydroxyxanthone derivatives: Effective agents against acetylcholinesterase
Menéndez, Cintia Anabella
XANTHONES
ACHE
MOLECULAR DYNAMICS
MOLECULAR DOCKING
title_short Design, synthesis and biological evaluation of 1,3-dihydroxyxanthone derivatives: Effective agents against acetylcholinesterase
title_full Design, synthesis and biological evaluation of 1,3-dihydroxyxanthone derivatives: Effective agents against acetylcholinesterase
title_fullStr Design, synthesis and biological evaluation of 1,3-dihydroxyxanthone derivatives: Effective agents against acetylcholinesterase
title_full_unstemmed Design, synthesis and biological evaluation of 1,3-dihydroxyxanthone derivatives: Effective agents against acetylcholinesterase
title_sort Design, synthesis and biological evaluation of 1,3-dihydroxyxanthone derivatives: Effective agents against acetylcholinesterase
dc.creator.none.fl_str_mv Menéndez, Cintia Anabella
Biscussi, Brunella
Accordino, Sebastian Roberto
Murray, Ana Paula
Gerbino, Darío César
Appignanesi, Gustavo Adrian
author Menéndez, Cintia Anabella
author_facet Menéndez, Cintia Anabella
Biscussi, Brunella
Accordino, Sebastian Roberto
Murray, Ana Paula
Gerbino, Darío César
Appignanesi, Gustavo Adrian
author_role author
author2 Biscussi, Brunella
Accordino, Sebastian Roberto
Murray, Ana Paula
Gerbino, Darío César
Appignanesi, Gustavo Adrian
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv XANTHONES
ACHE
MOLECULAR DYNAMICS
MOLECULAR DOCKING
topic XANTHONES
ACHE
MOLECULAR DYNAMICS
MOLECULAR DOCKING
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The present work concerns the rational design and development of new inhibitors of acetylcholinesterase (AChE) based on the privileged xanthone scaffold. In order to understand and rationalize the mode of action of these target structures a theoretical study was initially conducted. From the results of rational design, a new variety of amphiphilic xanthone derivatives were synthesized, structurally characterized and evaluated as potential anti-Alzheimer agents. The results showed that most of the synthesized compounds exhibited high AChE inhibitory activity at the micromolar range (IC50, 0.46–12.09 μM). The synthetic xanthone 11 showed the best inhibitory effect on AChE and a molecular modeling study revealed that 11 targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Therefore, this compound could be considered as a potential lead compound towards new drugs for the treatment of Alzheimer’s disease.
Fil: Menéndez, Cintia Anabella. 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
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
Fil: Accordino, Sebastian Roberto. 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
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
Fil: Gerbino, Darío César. 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
Fil: Appignanesi, Gustavo Adrian. 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
description The present work concerns the rational design and development of new inhibitors of acetylcholinesterase (AChE) based on the privileged xanthone scaffold. In order to understand and rationalize the mode of action of these target structures a theoretical study was initially conducted. From the results of rational design, a new variety of amphiphilic xanthone derivatives were synthesized, structurally characterized and evaluated as potential anti-Alzheimer agents. The results showed that most of the synthesized compounds exhibited high AChE inhibitory activity at the micromolar range (IC50, 0.46–12.09 μM). The synthetic xanthone 11 showed the best inhibitory effect on AChE and a molecular modeling study revealed that 11 targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Therefore, this compound could be considered as a potential lead compound towards new drugs for the treatment of Alzheimer’s disease.
publishDate 2017
dc.date.none.fl_str_mv 2017-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/42719
Menéndez, Cintia Anabella; Biscussi, Brunella; Accordino, Sebastian Roberto; Murray, Ana Paula; Gerbino, Darío César; et al.; Design, synthesis and biological evaluation of 1,3-dihydroxyxanthone derivatives: Effective agents against acetylcholinesterase; Academic Press Inc Elsevier Science; Bioorganic Chemistry; 75; 9-2017; 201-209
0045-2068
CONICET Digital
CONICET
url http://hdl.handle.net/11336/42719
identifier_str_mv Menéndez, Cintia Anabella; Biscussi, Brunella; Accordino, Sebastian Roberto; Murray, Ana Paula; Gerbino, Darío César; et al.; Design, synthesis and biological evaluation of 1,3-dihydroxyxanthone derivatives: Effective agents against acetylcholinesterase; Academic Press Inc Elsevier Science; Bioorganic Chemistry; 75; 9-2017; 201-209
0045-2068
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0045206817305527
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bioorg.2017.09.012
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Academic Press Inc Elsevier Science
publisher.none.fl_str_mv Academic Press Inc Elsevier Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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