An Integrated Molecular Approach to Predict Caffeine Analogs for Enhancing Cholinergic Signaling and Neuroprotection

Autores
Obiol, Diego Javier; Vietri, Agustin; Amundarain, María Julia; Zamarreño, Fernando; Costabel, Marcelo Daniel; Antollini, Silvia Susana
Año de publicación
2023
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
In our study, we designed forty-one caffeine analogs with the aim of improving the modulation of acetylcholinesterase (AchE, PDBid: 4EY7) and activating the neuronal nicotinic acetylcholine receptor (α7-nAchR, PDBid: 7EKI) more effectively than the prototype caffeine. The central purpose of this work was to enhance cholinergic neurotransmission. Analogue T-44 emerged as the most promising due to its high affinity for both targets. However, we expanded our analysis to assess the impact of all designed analogs on two other molecular targets: the muscle nicotinic acetylcholine receptor (PDBid: 7QL5) and the human adenosine receptor (hA2AR, PDBid: 3RFM), a G protein- coupled receptor, class A. Inhibition of hA2AR by caffeine could also offer potential benefits in terms of neuroprotection. We conducted a thorough analysis of the pharmacokinetic and molecular properties of each analog and performed molecular docking at the orthosteric sites of the targets to determine the binding affinity score. For the prediction of pharmacokinetic parameters, we used pkCSM and SwissADME, and for performing molecular docking, we employed AutoDock Vina. We compared these results with known compounds to identify potential candidates with a high potential to modulate the activity of multiple target molecules simultaneously. Our findings reveal that some analogs, in addition to the prominent T-44, emerge as potential candidates to enhance cholinergic activity and potentially provide neuroprotection. In future studies, we plan to carry out molecular dynamics simulations and in vitro analyses to confirm the effects of these analogs on molecular targets. This work presents qualitative structure-activity relationship studies that provide relevant information for the design of new molecules that could enhance neurotransmission and neuroprotection.
Fil: Obiol, Diego Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; Argentina
Fil: Vietri, Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; Argentina
Fil: Amundarain, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; Argentina
Fil: Zamarreño, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; Argentina
Fil: Costabel, Marcelo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; Argentina
Fil: Antollini, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
LI Reunión Anual de la Sociedad Argentina de Biofísica
Córdoba
Argentina
Sociedad de Biofísica Argentina
Materia
Señalizacion colinergica
Enfermedad de Alzheimer
Cafeína
Estudios in silico
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/250280
Acceder
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network_name_str CONICET Digital (CONICET)
spelling An Integrated Molecular Approach to Predict Caffeine Analogs for Enhancing Cholinergic Signaling and NeuroprotectionObiol, Diego JavierVietri, AgustinAmundarain, María JuliaZamarreño, FernandoCostabel, Marcelo DanielAntollini, Silvia SusanaSeñalizacion colinergicaEnfermedad de AlzheimerCafeínaEstudios in silicohttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1In our study, we designed forty-one caffeine analogs with the aim of improving the modulation of acetylcholinesterase (AchE, PDBid: 4EY7) and activating the neuronal nicotinic acetylcholine receptor (α7-nAchR, PDBid: 7EKI) more effectively than the prototype caffeine. The central purpose of this work was to enhance cholinergic neurotransmission. Analogue T-44 emerged as the most promising due to its high affinity for both targets. However, we expanded our analysis to assess the impact of all designed analogs on two other molecular targets: the muscle nicotinic acetylcholine receptor (PDBid: 7QL5) and the human adenosine receptor (hA2AR, PDBid: 3RFM), a G protein- coupled receptor, class A. Inhibition of hA2AR by caffeine could also offer potential benefits in terms of neuroprotection. We conducted a thorough analysis of the pharmacokinetic and molecular properties of each analog and performed molecular docking at the orthosteric sites of the targets to determine the binding affinity score. For the prediction of pharmacokinetic parameters, we used pkCSM and SwissADME, and for performing molecular docking, we employed AutoDock Vina. We compared these results with known compounds to identify potential candidates with a high potential to modulate the activity of multiple target molecules simultaneously. Our findings reveal that some analogs, in addition to the prominent T-44, emerge as potential candidates to enhance cholinergic activity and potentially provide neuroprotection. In future studies, we plan to carry out molecular dynamics simulations and in vitro analyses to confirm the effects of these analogs on molecular targets. This work presents qualitative structure-activity relationship studies that provide relevant information for the design of new molecules that could enhance neurotransmission and neuroprotection.Fil: Obiol, Diego Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; ArgentinaFil: Vietri, Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; ArgentinaFil: Amundarain, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; ArgentinaFil: Zamarreño, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; ArgentinaFil: Costabel, Marcelo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; ArgentinaFil: Antollini, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaLI Reunión Anual de la Sociedad Argentina de BiofísicaCórdobaArgentinaSociedad de Biofísica ArgentinaSociedad Argentina de Biofísica2023info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/250280An Integrated Molecular Approach to Predict Caffeine Analogs for Enhancing Cholinergic Signaling and Neuroprotection; LI Reunión Anual de la Sociedad Argentina de Biofísica; Córdoba; Argentina; 2023; 105-105978-987-48938-1-9CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://biofisica.org.ar/reuniones-cientificas/reunionsab-previas/Internacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:43:21Zoai:ri.conicet.gov.ar:11336/250280instacron: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:34982025-09-03 09:43:21.262CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv An Integrated Molecular Approach to Predict Caffeine Analogs for Enhancing Cholinergic Signaling and Neuroprotection
title An Integrated Molecular Approach to Predict Caffeine Analogs for Enhancing Cholinergic Signaling and Neuroprotection
spellingShingle An Integrated Molecular Approach to Predict Caffeine Analogs for Enhancing Cholinergic Signaling and Neuroprotection
Obiol, Diego Javier
Señalizacion colinergica
Enfermedad de Alzheimer
Cafeína
Estudios in silico
title_short An Integrated Molecular Approach to Predict Caffeine Analogs for Enhancing Cholinergic Signaling and Neuroprotection
title_full An Integrated Molecular Approach to Predict Caffeine Analogs for Enhancing Cholinergic Signaling and Neuroprotection
title_fullStr An Integrated Molecular Approach to Predict Caffeine Analogs for Enhancing Cholinergic Signaling and Neuroprotection
title_full_unstemmed An Integrated Molecular Approach to Predict Caffeine Analogs for Enhancing Cholinergic Signaling and Neuroprotection
title_sort An Integrated Molecular Approach to Predict Caffeine Analogs for Enhancing Cholinergic Signaling and Neuroprotection
dc.creator.none.fl_str_mv Obiol, Diego Javier
Vietri, Agustin
Amundarain, María Julia
Zamarreño, Fernando
Costabel, Marcelo Daniel
Antollini, Silvia Susana
author Obiol, Diego Javier
author_facet Obiol, Diego Javier
Vietri, Agustin
Amundarain, María Julia
Zamarreño, Fernando
Costabel, Marcelo Daniel
Antollini, Silvia Susana
author_role author
author2 Vietri, Agustin
Amundarain, María Julia
Zamarreño, Fernando
Costabel, Marcelo Daniel
Antollini, Silvia Susana
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Señalizacion colinergica
Enfermedad de Alzheimer
Cafeína
Estudios in silico
topic Señalizacion colinergica
Enfermedad de Alzheimer
Cafeína
Estudios in silico
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv In our study, we designed forty-one caffeine analogs with the aim of improving the modulation of acetylcholinesterase (AchE, PDBid: 4EY7) and activating the neuronal nicotinic acetylcholine receptor (α7-nAchR, PDBid: 7EKI) more effectively than the prototype caffeine. The central purpose of this work was to enhance cholinergic neurotransmission. Analogue T-44 emerged as the most promising due to its high affinity for both targets. However, we expanded our analysis to assess the impact of all designed analogs on two other molecular targets: the muscle nicotinic acetylcholine receptor (PDBid: 7QL5) and the human adenosine receptor (hA2AR, PDBid: 3RFM), a G protein- coupled receptor, class A. Inhibition of hA2AR by caffeine could also offer potential benefits in terms of neuroprotection. We conducted a thorough analysis of the pharmacokinetic and molecular properties of each analog and performed molecular docking at the orthosteric sites of the targets to determine the binding affinity score. For the prediction of pharmacokinetic parameters, we used pkCSM and SwissADME, and for performing molecular docking, we employed AutoDock Vina. We compared these results with known compounds to identify potential candidates with a high potential to modulate the activity of multiple target molecules simultaneously. Our findings reveal that some analogs, in addition to the prominent T-44, emerge as potential candidates to enhance cholinergic activity and potentially provide neuroprotection. In future studies, we plan to carry out molecular dynamics simulations and in vitro analyses to confirm the effects of these analogs on molecular targets. This work presents qualitative structure-activity relationship studies that provide relevant information for the design of new molecules that could enhance neurotransmission and neuroprotection.
Fil: Obiol, Diego Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; Argentina
Fil: Vietri, Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; Argentina
Fil: Amundarain, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; Argentina
Fil: Zamarreño, Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; Argentina
Fil: Costabel, Marcelo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Física del Sur. Universidad Nacional del Sur. Departamento de Física. Instituto de Física del Sur; Argentina
Fil: Antollini, Silvia Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Investigaciones Bioquímicas de Bahía Blanca. Universidad Nacional del Sur. Instituto de Investigaciones Bioquímicas de Bahía Blanca; Argentina. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; Argentina
LI Reunión Anual de la Sociedad Argentina de Biofísica
Córdoba
Argentina
Sociedad de Biofísica Argentina
description In our study, we designed forty-one caffeine analogs with the aim of improving the modulation of acetylcholinesterase (AchE, PDBid: 4EY7) and activating the neuronal nicotinic acetylcholine receptor (α7-nAchR, PDBid: 7EKI) more effectively than the prototype caffeine. The central purpose of this work was to enhance cholinergic neurotransmission. Analogue T-44 emerged as the most promising due to its high affinity for both targets. However, we expanded our analysis to assess the impact of all designed analogs on two other molecular targets: the muscle nicotinic acetylcholine receptor (PDBid: 7QL5) and the human adenosine receptor (hA2AR, PDBid: 3RFM), a G protein- coupled receptor, class A. Inhibition of hA2AR by caffeine could also offer potential benefits in terms of neuroprotection. We conducted a thorough analysis of the pharmacokinetic and molecular properties of each analog and performed molecular docking at the orthosteric sites of the targets to determine the binding affinity score. For the prediction of pharmacokinetic parameters, we used pkCSM and SwissADME, and for performing molecular docking, we employed AutoDock Vina. We compared these results with known compounds to identify potential candidates with a high potential to modulate the activity of multiple target molecules simultaneously. Our findings reveal that some analogs, in addition to the prominent T-44, emerge as potential candidates to enhance cholinergic activity and potentially provide neuroprotection. In future studies, we plan to carry out molecular dynamics simulations and in vitro analyses to confirm the effects of these analogs on molecular targets. This work presents qualitative structure-activity relationship studies that provide relevant information for the design of new molecules that could enhance neurotransmission and neuroprotection.
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Reunión
Book
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/250280
An Integrated Molecular Approach to Predict Caffeine Analogs for Enhancing Cholinergic Signaling and Neuroprotection; LI Reunión Anual de la Sociedad Argentina de Biofísica; Córdoba; Argentina; 2023; 105-105
978-987-48938-1-9
CONICET Digital
CONICET
url http://hdl.handle.net/11336/250280
identifier_str_mv An Integrated Molecular Approach to Predict Caffeine Analogs for Enhancing Cholinergic Signaling and Neuroprotection; LI Reunión Anual de la Sociedad Argentina de Biofísica; Córdoba; Argentina; 2023; 105-105
978-987-48938-1-9
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://biofisica.org.ar/reuniones-cientificas/reunionsab-previas/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.coverage.none.fl_str_mv Internacional
dc.publisher.none.fl_str_mv Sociedad Argentina de Biofísica
publisher.none.fl_str_mv Sociedad Argentina de Biofísica
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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