Novel Butyrylcholinesterase Inhibitor Alkaloids from Cannabis sativa Roots: Bioguided Isolation and In Silico Study

Autores
Ortiz, Javier Esteban; Adarvez Feresin, Camila Wadía; Llalla Cordova, Olimpia; Cristos, Diego Sebastián; Garro, Adriana; Feresin, Gabriela Egly
Año de publicación
2025
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Neurodegenerative diseases, including Alzheimer’s disease (AD), represent one of the main global health challenges. Cannabis sativa synthesizes spermidine-type alkaloids, whose potential biological activities have been little studied. This study aimed to isolate bioactive alkaloids from an alkaloid-enriched extract (AEE) of C. sativa roots throughout a bioguided approach using conventional chromatographic techniques based on AChE and BuChE inhibitory activities. A qualitative and semiquantitative analysis by UPLC-ESI-MS/MS as well as molecular modeling simulations were performed. In addition, predictive in silico analyses were conducted to assess toxicity properties. The alkaloids cannabisativine (CS) and anhydrocannabisativine (ACS) were isolated, and showed highly selective BuChE inhibitory activity. The molecular modeling study revealed a conserved interaction profile across both alkaloids, indicating the amino acids TRP82, GLU197, TYR440, and HIS438 as the major contributors involved in the complex formation. Finally, CS and ACS exhibited low in silico predictive toxicity values. In conclusion, CS and ACS alkaloids emerge as new selective BuChE inhibitors with therapeutic potential that deserves the attention from the field of pharmacology in neurodegenerative disease research. Additionally, this approach promotes innovation and environmental sustainability through the use of C. sativa roots.
Fil: Ortiz, Javier Esteban. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; Argentina
Fil: Adarvez Feresin, Camila Wadía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Llalla Cordova, Olimpia. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; Argentina
Fil: Cristos, Diego Sebastián. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación de Agroindustria. Instituto de Tecnología de Alimentos; Argentina
Fil: Garro, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Feresin, Gabriela Egly. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; Argentina. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; Argentina
Materia
CANNABIS SATIVA ROOTS
SPERMIDINE ALKALOIDS
BUTYRYLCHOLINESTERASE
CANNABISATIVINE
ANHYDROCANNABISATIVINE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/274535
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/274535
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Novel Butyrylcholinesterase Inhibitor Alkaloids from Cannabis sativa Roots: Bioguided Isolation and In Silico StudyOrtiz, Javier EstebanAdarvez Feresin, Camila WadíaLlalla Cordova, OlimpiaCristos, Diego SebastiánGarro, AdrianaFeresin, Gabriela EglyCANNABIS SATIVA ROOTSSPERMIDINE ALKALOIDSBUTYRYLCHOLINESTERASECANNABISATIVINEANHYDROCANNABISATIVINEhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Neurodegenerative diseases, including Alzheimer’s disease (AD), represent one of the main global health challenges. Cannabis sativa synthesizes spermidine-type alkaloids, whose potential biological activities have been little studied. This study aimed to isolate bioactive alkaloids from an alkaloid-enriched extract (AEE) of C. sativa roots throughout a bioguided approach using conventional chromatographic techniques based on AChE and BuChE inhibitory activities. A qualitative and semiquantitative analysis by UPLC-ESI-MS/MS as well as molecular modeling simulations were performed. In addition, predictive in silico analyses were conducted to assess toxicity properties. The alkaloids cannabisativine (CS) and anhydrocannabisativine (ACS) were isolated, and showed highly selective BuChE inhibitory activity. The molecular modeling study revealed a conserved interaction profile across both alkaloids, indicating the amino acids TRP82, GLU197, TYR440, and HIS438 as the major contributors involved in the complex formation. Finally, CS and ACS exhibited low in silico predictive toxicity values. In conclusion, CS and ACS alkaloids emerge as new selective BuChE inhibitors with therapeutic potential that deserves the attention from the field of pharmacology in neurodegenerative disease research. Additionally, this approach promotes innovation and environmental sustainability through the use of C. sativa roots.Fil: Ortiz, Javier Esteban. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; ArgentinaFil: Adarvez Feresin, Camila Wadía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Llalla Cordova, Olimpia. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; ArgentinaFil: Cristos, Diego Sebastián. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación de Agroindustria. Instituto de Tecnología de Alimentos; ArgentinaFil: Garro, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Feresin, Gabriela Egly. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; Argentina. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; ArgentinaMDPI2025-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/274535Ortiz, Javier Esteban; Adarvez Feresin, Camila Wadía; Llalla Cordova, Olimpia; Cristos, Diego Sebastián; Garro, Adriana; et al.; Novel Butyrylcholinesterase Inhibitor Alkaloids from Cannabis sativa Roots: Bioguided Isolation and In Silico Study; MDPI; Compounds; 5; 3; 9-2025; 1-152673-6918CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2673-6918/5/3/35info:eu-repo/semantics/altIdentifier/doi/10.3390/compounds5030035info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-12-03T08:50:31Zoai:ri.conicet.gov.ar:11336/274535instacron: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:34982025-12-03 08:50:32.045CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Novel Butyrylcholinesterase Inhibitor Alkaloids from Cannabis sativa Roots: Bioguided Isolation and In Silico Study
title Novel Butyrylcholinesterase Inhibitor Alkaloids from Cannabis sativa Roots: Bioguided Isolation and In Silico Study
spellingShingle Novel Butyrylcholinesterase Inhibitor Alkaloids from Cannabis sativa Roots: Bioguided Isolation and In Silico Study
Ortiz, Javier Esteban
CANNABIS SATIVA ROOTS
SPERMIDINE ALKALOIDS
BUTYRYLCHOLINESTERASE
CANNABISATIVINE
ANHYDROCANNABISATIVINE
title_short Novel Butyrylcholinesterase Inhibitor Alkaloids from Cannabis sativa Roots: Bioguided Isolation and In Silico Study
title_full Novel Butyrylcholinesterase Inhibitor Alkaloids from Cannabis sativa Roots: Bioguided Isolation and In Silico Study
title_fullStr Novel Butyrylcholinesterase Inhibitor Alkaloids from Cannabis sativa Roots: Bioguided Isolation and In Silico Study
title_full_unstemmed Novel Butyrylcholinesterase Inhibitor Alkaloids from Cannabis sativa Roots: Bioguided Isolation and In Silico Study
title_sort Novel Butyrylcholinesterase Inhibitor Alkaloids from Cannabis sativa Roots: Bioguided Isolation and In Silico Study
dc.creator.none.fl_str_mv Ortiz, Javier Esteban
Adarvez Feresin, Camila Wadía
Llalla Cordova, Olimpia
Cristos, Diego Sebastián
Garro, Adriana
Feresin, Gabriela Egly
author Ortiz, Javier Esteban
author_facet Ortiz, Javier Esteban
Adarvez Feresin, Camila Wadía
Llalla Cordova, Olimpia
Cristos, Diego Sebastián
Garro, Adriana
Feresin, Gabriela Egly
author_role author
author2 Adarvez Feresin, Camila Wadía
Llalla Cordova, Olimpia
Cristos, Diego Sebastián
Garro, Adriana
Feresin, Gabriela Egly
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv CANNABIS SATIVA ROOTS
SPERMIDINE ALKALOIDS
BUTYRYLCHOLINESTERASE
CANNABISATIVINE
ANHYDROCANNABISATIVINE
topic CANNABIS SATIVA ROOTS
SPERMIDINE ALKALOIDS
BUTYRYLCHOLINESTERASE
CANNABISATIVINE
ANHYDROCANNABISATIVINE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Neurodegenerative diseases, including Alzheimer’s disease (AD), represent one of the main global health challenges. Cannabis sativa synthesizes spermidine-type alkaloids, whose potential biological activities have been little studied. This study aimed to isolate bioactive alkaloids from an alkaloid-enriched extract (AEE) of C. sativa roots throughout a bioguided approach using conventional chromatographic techniques based on AChE and BuChE inhibitory activities. A qualitative and semiquantitative analysis by UPLC-ESI-MS/MS as well as molecular modeling simulations were performed. In addition, predictive in silico analyses were conducted to assess toxicity properties. The alkaloids cannabisativine (CS) and anhydrocannabisativine (ACS) were isolated, and showed highly selective BuChE inhibitory activity. The molecular modeling study revealed a conserved interaction profile across both alkaloids, indicating the amino acids TRP82, GLU197, TYR440, and HIS438 as the major contributors involved in the complex formation. Finally, CS and ACS exhibited low in silico predictive toxicity values. In conclusion, CS and ACS alkaloids emerge as new selective BuChE inhibitors with therapeutic potential that deserves the attention from the field of pharmacology in neurodegenerative disease research. Additionally, this approach promotes innovation and environmental sustainability through the use of C. sativa roots.
Fil: Ortiz, Javier Esteban. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; Argentina
Fil: Adarvez Feresin, Camila Wadía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Llalla Cordova, Olimpia. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; Argentina
Fil: Cristos, Diego Sebastián. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación de Agroindustria. Instituto de Tecnología de Alimentos; Argentina
Fil: Garro, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Feresin, Gabriela Egly. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan; Argentina. Universidad Nacional de San Juan. Facultad de Ingeniería. Instituto de Biotecnología; Argentina
description Neurodegenerative diseases, including Alzheimer’s disease (AD), represent one of the main global health challenges. Cannabis sativa synthesizes spermidine-type alkaloids, whose potential biological activities have been little studied. This study aimed to isolate bioactive alkaloids from an alkaloid-enriched extract (AEE) of C. sativa roots throughout a bioguided approach using conventional chromatographic techniques based on AChE and BuChE inhibitory activities. A qualitative and semiquantitative analysis by UPLC-ESI-MS/MS as well as molecular modeling simulations were performed. In addition, predictive in silico analyses were conducted to assess toxicity properties. The alkaloids cannabisativine (CS) and anhydrocannabisativine (ACS) were isolated, and showed highly selective BuChE inhibitory activity. The molecular modeling study revealed a conserved interaction profile across both alkaloids, indicating the amino acids TRP82, GLU197, TYR440, and HIS438 as the major contributors involved in the complex formation. Finally, CS and ACS exhibited low in silico predictive toxicity values. In conclusion, CS and ACS alkaloids emerge as new selective BuChE inhibitors with therapeutic potential that deserves the attention from the field of pharmacology in neurodegenerative disease research. Additionally, this approach promotes innovation and environmental sustainability through the use of C. sativa roots.
publishDate 2025
dc.date.none.fl_str_mv 2025-09
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/11336/274535
Ortiz, Javier Esteban; Adarvez Feresin, Camila Wadía; Llalla Cordova, Olimpia; Cristos, Diego Sebastián; Garro, Adriana; et al.; Novel Butyrylcholinesterase Inhibitor Alkaloids from Cannabis sativa Roots: Bioguided Isolation and In Silico Study; MDPI; Compounds; 5; 3; 9-2025; 1-15
2673-6918
CONICET Digital
CONICET
url http://hdl.handle.net/11336/274535
identifier_str_mv Ortiz, Javier Esteban; Adarvez Feresin, Camila Wadía; Llalla Cordova, Olimpia; Cristos, Diego Sebastián; Garro, Adriana; et al.; Novel Butyrylcholinesterase Inhibitor Alkaloids from Cannabis sativa Roots: Bioguided Isolation and In Silico Study; MDPI; Compounds; 5; 3; 9-2025; 1-15
2673-6918
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.mdpi.com/2673-6918/5/3/35
info:eu-repo/semantics/altIdentifier/doi/10.3390/compounds5030035
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
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 13.214268

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