N-methyl-β-carboline alkaloids: structure-dependent photosensitizing properties and localization in subcellular domains

Autores
Denofrio, Maria Paula; Rasse Suriani, Federico Ariel Osvaldo; Paredes, Jose M.; Fassetta, Federico; Crovetto, Luis; Giron, Maria D.; Salto, Rafael; Epe, Bernd; Cabrerizo, Franco Martín
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
N-methyl-Beta-carboline (bC) alkaloids, including normelinonine F and melinonine F, have been found in a vast range of living species playing different biological, biomedical and/or pharmacological roles. Despite this, molecular bases of the mechanisms through which these alkaloids would exert their effect still remain unknown. Fundamental aspects including the photosensitizing properties and intracellular internalization of a selected group of N-methyl-bC alkaloids were investigated herein. Data reveal that methylation of the bC main ring enhances its photosensitizing properties either by increasing its binding affinity with DNA as biomolecular target and/or by increasing its oxidation potential, in a structure dependent manner. As a general rule, N(9)-substituted bCs showed the highest photosensitizing efficiency. With the exception of 2-methyl-harminium, all the N-methyl-bCs investigated herein induce a similar DNA photodamage profile, dominated largely by oxidized purines. This fact represents a distinctive behavior when comparing with N-unsubstituted-bCs. On the other hand, although all the investigated compounds might accumulate mainly into the mitochondria of HeLa cells, methylation provides a distinctive dynamic pattern for mitochondrial uptake. While rapid (passive) diffusion is most probably reponsible for the prompt uptake/release of neutral bCs, an active transport appears to mediate the (reatively slow) uptake of the quaternary cationic bCs. This might be a consequence of a distinctive subcellular localization (mitochondrial membrane and/or matrix) or interaction with intracellular components. Biomedical and biotechnological implications are also discussed herein.
Fil: Denofrio, Maria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
Fil: Rasse Suriani, Federico Ariel Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina
Fil: Paredes, Jose M.. Universidad de Granada. Facultad de Farmacia. Departamento de Fisicoquimica.; España
Fil: Fassetta, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
Fil: Crovetto, Luis. Universidad de Granada. Facultad de Farmacia. Departamento de Fisicoquimica.; España
Fil: Giron, Maria D.. Universidad de Granada. Facultad de Farmacia.; España
Fil: Salto, Rafael. Universidad de Granada. Facultad de Farmacia.; España
Fil: Epe, Bernd. Johannes Gutenberg Universitat Mainz; Alemania
Fil: Cabrerizo, Franco Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
Materia
N-METHYL-BETA-CARBOLINE
PHOTOSENSITIZING-PROPERTIES
INTRACELLULAR
INTERNALIZATION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/157812
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/157812
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling N-methyl-β-carboline alkaloids: structure-dependent photosensitizing properties and localization in subcellular domainsDenofrio, Maria PaulaRasse Suriani, Federico Ariel OsvaldoParedes, Jose M.Fassetta, FedericoCrovetto, LuisGiron, Maria D.Salto, RafaelEpe, BerndCabrerizo, Franco MartínN-METHYL-BETA-CARBOLINEPHOTOSENSITIZING-PROPERTIESINTRACELLULARINTERNALIZATIONhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1N-methyl-Beta-carboline (bC) alkaloids, including normelinonine F and melinonine F, have been found in a vast range of living species playing different biological, biomedical and/or pharmacological roles. Despite this, molecular bases of the mechanisms through which these alkaloids would exert their effect still remain unknown. Fundamental aspects including the photosensitizing properties and intracellular internalization of a selected group of N-methyl-bC alkaloids were investigated herein. Data reveal that methylation of the bC main ring enhances its photosensitizing properties either by increasing its binding affinity with DNA as biomolecular target and/or by increasing its oxidation potential, in a structure dependent manner. As a general rule, N(9)-substituted bCs showed the highest photosensitizing efficiency. With the exception of 2-methyl-harminium, all the N-methyl-bCs investigated herein induce a similar DNA photodamage profile, dominated largely by oxidized purines. This fact represents a distinctive behavior when comparing with N-unsubstituted-bCs. On the other hand, although all the investigated compounds might accumulate mainly into the mitochondria of HeLa cells, methylation provides a distinctive dynamic pattern for mitochondrial uptake. While rapid (passive) diffusion is most probably reponsible for the prompt uptake/release of neutral bCs, an active transport appears to mediate the (reatively slow) uptake of the quaternary cationic bCs. This might be a consequence of a distinctive subcellular localization (mitochondrial membrane and/or matrix) or interaction with intracellular components. Biomedical and biotechnological implications are also discussed herein.Fil: Denofrio, Maria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Rasse Suriani, Federico Ariel Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; ArgentinaFil: Paredes, Jose M.. Universidad de Granada. Facultad de Farmacia. Departamento de Fisicoquimica.; EspañaFil: Fassetta, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaFil: Crovetto, Luis. Universidad de Granada. Facultad de Farmacia. Departamento de Fisicoquimica.; EspañaFil: Giron, Maria D.. Universidad de Granada. Facultad de Farmacia.; EspañaFil: Salto, Rafael. Universidad de Granada. Facultad de Farmacia.; EspañaFil: Epe, Bernd. Johannes Gutenberg Universitat Mainz; AlemaniaFil: Cabrerizo, Franco Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); ArgentinaRoyal Society of Chemistry2020-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/157812Denofrio, Maria Paula; Rasse Suriani, Federico Ariel Osvaldo; Paredes, Jose M.; Fassetta, Federico; Crovetto, Luis; et al.; N-methyl-β-carboline alkaloids: structure-dependent photosensitizing properties and localization in subcellular domains; Royal Society of Chemistry; Organic & Biomolecular Chemistry; 33; 7-2020; 1-121477-0520CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1039/d0ob01122cinfo:eu-repo/semantics/altIdentifier/url/https://pubs.rsc.org/en/content/articlelanding/2020/OB/D0OB01122Cinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:17:44Zoai:ri.conicet.gov.ar:11336/157812instacron: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:34982025-09-10 13:17:44.69CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv N-methyl-β-carboline alkaloids: structure-dependent photosensitizing properties and localization in subcellular domains
title N-methyl-β-carboline alkaloids: structure-dependent photosensitizing properties and localization in subcellular domains
spellingShingle N-methyl-β-carboline alkaloids: structure-dependent photosensitizing properties and localization in subcellular domains
Denofrio, Maria Paula
N-METHYL-BETA-CARBOLINE
PHOTOSENSITIZING-PROPERTIES
INTRACELLULAR
INTERNALIZATION
title_short N-methyl-β-carboline alkaloids: structure-dependent photosensitizing properties and localization in subcellular domains
title_full N-methyl-β-carboline alkaloids: structure-dependent photosensitizing properties and localization in subcellular domains
title_fullStr N-methyl-β-carboline alkaloids: structure-dependent photosensitizing properties and localization in subcellular domains
title_full_unstemmed N-methyl-β-carboline alkaloids: structure-dependent photosensitizing properties and localization in subcellular domains
title_sort N-methyl-β-carboline alkaloids: structure-dependent photosensitizing properties and localization in subcellular domains
dc.creator.none.fl_str_mv Denofrio, Maria Paula
Rasse Suriani, Federico Ariel Osvaldo
Paredes, Jose M.
Fassetta, Federico
Crovetto, Luis
Giron, Maria D.
Salto, Rafael
Epe, Bernd
Cabrerizo, Franco Martín
author Denofrio, Maria Paula
author_facet Denofrio, Maria Paula
Rasse Suriani, Federico Ariel Osvaldo
Paredes, Jose M.
Fassetta, Federico
Crovetto, Luis
Giron, Maria D.
Salto, Rafael
Epe, Bernd
Cabrerizo, Franco Martín
author_role author
author2 Rasse Suriani, Federico Ariel Osvaldo
Paredes, Jose M.
Fassetta, Federico
Crovetto, Luis
Giron, Maria D.
Salto, Rafael
Epe, Bernd
Cabrerizo, Franco Martín
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv N-METHYL-BETA-CARBOLINE
PHOTOSENSITIZING-PROPERTIES
INTRACELLULAR
INTERNALIZATION
topic N-METHYL-BETA-CARBOLINE
PHOTOSENSITIZING-PROPERTIES
INTRACELLULAR
INTERNALIZATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv N-methyl-Beta-carboline (bC) alkaloids, including normelinonine F and melinonine F, have been found in a vast range of living species playing different biological, biomedical and/or pharmacological roles. Despite this, molecular bases of the mechanisms through which these alkaloids would exert their effect still remain unknown. Fundamental aspects including the photosensitizing properties and intracellular internalization of a selected group of N-methyl-bC alkaloids were investigated herein. Data reveal that methylation of the bC main ring enhances its photosensitizing properties either by increasing its binding affinity with DNA as biomolecular target and/or by increasing its oxidation potential, in a structure dependent manner. As a general rule, N(9)-substituted bCs showed the highest photosensitizing efficiency. With the exception of 2-methyl-harminium, all the N-methyl-bCs investigated herein induce a similar DNA photodamage profile, dominated largely by oxidized purines. This fact represents a distinctive behavior when comparing with N-unsubstituted-bCs. On the other hand, although all the investigated compounds might accumulate mainly into the mitochondria of HeLa cells, methylation provides a distinctive dynamic pattern for mitochondrial uptake. While rapid (passive) diffusion is most probably reponsible for the prompt uptake/release of neutral bCs, an active transport appears to mediate the (reatively slow) uptake of the quaternary cationic bCs. This might be a consequence of a distinctive subcellular localization (mitochondrial membrane and/or matrix) or interaction with intracellular components. Biomedical and biotechnological implications are also discussed herein.
Fil: Denofrio, Maria Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
Fil: Rasse Suriani, Federico Ariel Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas; Argentina
Fil: Paredes, Jose M.. Universidad de Granada. Facultad de Farmacia. Departamento de Fisicoquimica.; España
Fil: Fassetta, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
Fil: Crovetto, Luis. Universidad de Granada. Facultad de Farmacia. Departamento de Fisicoquimica.; España
Fil: Giron, Maria D.. Universidad de Granada. Facultad de Farmacia.; España
Fil: Salto, Rafael. Universidad de Granada. Facultad de Farmacia.; España
Fil: Epe, Bernd. Johannes Gutenberg Universitat Mainz; Alemania
Fil: Cabrerizo, Franco Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús). Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas "Dr. Raúl Alfonsín" (sede Chascomús); Argentina
description N-methyl-Beta-carboline (bC) alkaloids, including normelinonine F and melinonine F, have been found in a vast range of living species playing different biological, biomedical and/or pharmacological roles. Despite this, molecular bases of the mechanisms through which these alkaloids would exert their effect still remain unknown. Fundamental aspects including the photosensitizing properties and intracellular internalization of a selected group of N-methyl-bC alkaloids were investigated herein. Data reveal that methylation of the bC main ring enhances its photosensitizing properties either by increasing its binding affinity with DNA as biomolecular target and/or by increasing its oxidation potential, in a structure dependent manner. As a general rule, N(9)-substituted bCs showed the highest photosensitizing efficiency. With the exception of 2-methyl-harminium, all the N-methyl-bCs investigated herein induce a similar DNA photodamage profile, dominated largely by oxidized purines. This fact represents a distinctive behavior when comparing with N-unsubstituted-bCs. On the other hand, although all the investigated compounds might accumulate mainly into the mitochondria of HeLa cells, methylation provides a distinctive dynamic pattern for mitochondrial uptake. While rapid (passive) diffusion is most probably reponsible for the prompt uptake/release of neutral bCs, an active transport appears to mediate the (reatively slow) uptake of the quaternary cationic bCs. This might be a consequence of a distinctive subcellular localization (mitochondrial membrane and/or matrix) or interaction with intracellular components. Biomedical and biotechnological implications are also discussed herein.
publishDate 2020
dc.date.none.fl_str_mv 2020-07
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/11336/157812
Denofrio, Maria Paula; Rasse Suriani, Federico Ariel Osvaldo; Paredes, Jose M.; Fassetta, Federico; Crovetto, Luis; et al.; N-methyl-β-carboline alkaloids: structure-dependent photosensitizing properties and localization in subcellular domains; Royal Society of Chemistry; Organic & Biomolecular Chemistry; 33; 7-2020; 1-12
1477-0520
CONICET Digital
CONICET
url http://hdl.handle.net/11336/157812
identifier_str_mv Denofrio, Maria Paula; Rasse Suriani, Federico Ariel Osvaldo; Paredes, Jose M.; Fassetta, Federico; Crovetto, Luis; et al.; N-methyl-β-carboline alkaloids: structure-dependent photosensitizing properties and localization in subcellular domains; Royal Society of Chemistry; Organic & Biomolecular Chemistry; 33; 7-2020; 1-12
1477-0520
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1039/d0ob01122c
info:eu-repo/semantics/altIdentifier/url/https://pubs.rsc.org/en/content/articlelanding/2020/OB/D0OB01122C
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Royal Society of Chemistry
publisher.none.fl_str_mv Royal Society of Chemistry
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 12.993085

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