Mechanisms of DNA damage by photoexcited 9-methyl-β-carbolines

Autores
Vignoni, Mariana; Rasse Suriani, Federico Ariel Osvaldo; Butzbach, Kathrin; Erra Balsells, Rosa; Epe, Bernd; Cabrerizo, Franco Martín
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
It has been well documented that β-carboline alkaloids, particularly the 9-methyl derivatives, are efficient photosensitizers. However, structure–activity relationships are missing and the photochemical mechanisms involved in the DNA photodamage still remain unknown. In the present work, we examined the capability of three 9-methyl-β-carbolines (9-methyl-norharmane, 9-methyl-harmane and 9-methylharmine) to induce DNA damage upon UVA excitation at physiological pH. The type and extent of the damage was analyzed together with the photophysical and binding properties of the β-carboline derivatives investigated. The results indicate that even at neutral pH most of the DNA damage is generated from the protonated form of the excited β-carbolines in a type-I reaction. Oxidized purine residues are produced in high excess over oxidized pyrimidines, single-strand breaks and sites of base loss. In addition, the excited neutral form of the β-carbolines is responsible for significant generation of cyclobutane pyrimidine dimers (CPDs) by triplet–triplet-energy transfer. In the case of 9-methyl-norharmane, the yield of CPDs is increased in D2O, probably due to less rapid protonation in the deuterated solvent.
Fil: Vignoni, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús. Instituto de Investigaciones Biotecnológicas (sede Chascomús); Argentina
Fil: Rasse Suriani, Federico Ariel Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús. Instituto de Investigaciones Biotecnológicas (sede Chascomús); Argentina
Fil: Butzbach, Kathrin. No especifíca;
Fil: Erra Balsells, Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono; Argentina
Fil: Epe, Bernd. No especifíca;
Fil: Cabrerizo, Franco Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús. Instituto de Investigaciones Biotecnológicas (sede Chascomús); Argentina
Materia
9-Methyl-B-Carbolines
Dna
Photosensitization
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:11336/2178
Acceder
id CONICETDig_d50f15ae55291e56846b7f5c81a77995
oai_identifier_str oai:ri.conicet.gov.ar:11336/2178
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Mechanisms of DNA damage by photoexcited 9-methyl-β-carbolinesVignoni, MarianaRasse Suriani, Federico Ariel OsvaldoButzbach, KathrinErra Balsells, RosaEpe, BerndCabrerizo, Franco Martín9-Methyl-B-CarbolinesDnaPhotosensitizationhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1It has been well documented that β-carboline alkaloids, particularly the 9-methyl derivatives, are efficient photosensitizers. However, structure–activity relationships are missing and the photochemical mechanisms involved in the DNA photodamage still remain unknown. In the present work, we examined the capability of three 9-methyl-β-carbolines (9-methyl-norharmane, 9-methyl-harmane and 9-methylharmine) to induce DNA damage upon UVA excitation at physiological pH. The type and extent of the damage was analyzed together with the photophysical and binding properties of the β-carboline derivatives investigated. The results indicate that even at neutral pH most of the DNA damage is generated from the protonated form of the excited β-carbolines in a type-I reaction. Oxidized purine residues are produced in high excess over oxidized pyrimidines, single-strand breaks and sites of base loss. In addition, the excited neutral form of the β-carbolines is responsible for significant generation of cyclobutane pyrimidine dimers (CPDs) by triplet–triplet-energy transfer. In the case of 9-methyl-norharmane, the yield of CPDs is increased in D2O, probably due to less rapid protonation in the deuterated solvent.Fil: Vignoni, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús. Instituto de Investigaciones Biotecnológicas (sede Chascomús); ArgentinaFil: Rasse Suriani, Federico Ariel Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús. Instituto de Investigaciones Biotecnológicas (sede Chascomús); ArgentinaFil: Butzbach, Kathrin. No especifíca;Fil: Erra Balsells, Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono; ArgentinaFil: Epe, Bernd. No especifíca;Fil: Cabrerizo, Franco Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús. Instituto de Investigaciones Biotecnológicas (sede Chascomús); ArgentinaRoyal Society of Chemistry2013-06-18info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/2178Vignoni, Mariana; Rasse Suriani, Federico Ariel Osvaldo; Butzbach, Kathrin; Erra Balsells, Rosa; Epe, Bernd; et al.; Mechanisms of DNA damage by photoexcited 9-methyl-β-carbolines; Royal Society of Chemistry; Organic & Biomolecular Chemistry; 11; 32; 18-6-2013; 5300-53091477-0520enginfo:eu-repo/semantics/altIdentifier/url/http://pubs.rsc.org/en/Content/ArticleLanding/2013/OB/c3ob40344k#!divAbstractinfo:eu-repo/semantics/altIdentifier/doi/DOI:10.1039/C3OB40344Kinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:21:31Zoai:ri.conicet.gov.ar:11336/2178instacron: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 13:21:31.287CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Mechanisms of DNA damage by photoexcited 9-methyl-β-carbolines
title Mechanisms of DNA damage by photoexcited 9-methyl-β-carbolines
spellingShingle Mechanisms of DNA damage by photoexcited 9-methyl-β-carbolines
Vignoni, Mariana
9-Methyl-B-Carbolines
Dna
Photosensitization
title_short Mechanisms of DNA damage by photoexcited 9-methyl-β-carbolines
title_full Mechanisms of DNA damage by photoexcited 9-methyl-β-carbolines
title_fullStr Mechanisms of DNA damage by photoexcited 9-methyl-β-carbolines
title_full_unstemmed Mechanisms of DNA damage by photoexcited 9-methyl-β-carbolines
title_sort Mechanisms of DNA damage by photoexcited 9-methyl-β-carbolines
dc.creator.none.fl_str_mv Vignoni, Mariana
Rasse Suriani, Federico Ariel Osvaldo
Butzbach, Kathrin
Erra Balsells, Rosa
Epe, Bernd
Cabrerizo, Franco Martín
author Vignoni, Mariana
author_facet Vignoni, Mariana
Rasse Suriani, Federico Ariel Osvaldo
Butzbach, Kathrin
Erra Balsells, Rosa
Epe, Bernd
Cabrerizo, Franco Martín
author_role author
author2 Rasse Suriani, Federico Ariel Osvaldo
Butzbach, Kathrin
Erra Balsells, Rosa
Epe, Bernd
Cabrerizo, Franco Martín
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv 9-Methyl-B-Carbolines
Dna
Photosensitization
topic 9-Methyl-B-Carbolines
Dna
Photosensitization
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv It has been well documented that β-carboline alkaloids, particularly the 9-methyl derivatives, are efficient photosensitizers. However, structure–activity relationships are missing and the photochemical mechanisms involved in the DNA photodamage still remain unknown. In the present work, we examined the capability of three 9-methyl-β-carbolines (9-methyl-norharmane, 9-methyl-harmane and 9-methylharmine) to induce DNA damage upon UVA excitation at physiological pH. The type and extent of the damage was analyzed together with the photophysical and binding properties of the β-carboline derivatives investigated. The results indicate that even at neutral pH most of the DNA damage is generated from the protonated form of the excited β-carbolines in a type-I reaction. Oxidized purine residues are produced in high excess over oxidized pyrimidines, single-strand breaks and sites of base loss. In addition, the excited neutral form of the β-carbolines is responsible for significant generation of cyclobutane pyrimidine dimers (CPDs) by triplet–triplet-energy transfer. In the case of 9-methyl-norharmane, the yield of CPDs is increased in D2O, probably due to less rapid protonation in the deuterated solvent.
Fil: Vignoni, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús. Instituto de Investigaciones Biotecnológicas (sede Chascomús); Argentina
Fil: Rasse Suriani, Federico Ariel Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús. Instituto de Investigaciones Biotecnológicas (sede Chascomús); Argentina
Fil: Butzbach, Kathrin. No especifíca;
Fil: Erra Balsells, Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono; Argentina
Fil: Epe, Bernd. No especifíca;
Fil: Cabrerizo, Franco Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Instituto de Investigaciones Biotecnológicas - Instituto Tecnológico Chascomús. Instituto de Investigaciones Biotecnológicas (sede Chascomús); Argentina
description It has been well documented that β-carboline alkaloids, particularly the 9-methyl derivatives, are efficient photosensitizers. However, structure–activity relationships are missing and the photochemical mechanisms involved in the DNA photodamage still remain unknown. In the present work, we examined the capability of three 9-methyl-β-carbolines (9-methyl-norharmane, 9-methyl-harmane and 9-methylharmine) to induce DNA damage upon UVA excitation at physiological pH. The type and extent of the damage was analyzed together with the photophysical and binding properties of the β-carboline derivatives investigated. The results indicate that even at neutral pH most of the DNA damage is generated from the protonated form of the excited β-carbolines in a type-I reaction. Oxidized purine residues are produced in high excess over oxidized pyrimidines, single-strand breaks and sites of base loss. In addition, the excited neutral form of the β-carbolines is responsible for significant generation of cyclobutane pyrimidine dimers (CPDs) by triplet–triplet-energy transfer. In the case of 9-methyl-norharmane, the yield of CPDs is increased in D2O, probably due to less rapid protonation in the deuterated solvent.
publishDate 2013
dc.date.none.fl_str_mv 2013-06-18
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/11336/2178
Vignoni, Mariana; Rasse Suriani, Federico Ariel Osvaldo; Butzbach, Kathrin; Erra Balsells, Rosa; Epe, Bernd; et al.; Mechanisms of DNA damage by photoexcited 9-methyl-β-carbolines; Royal Society of Chemistry; Organic & Biomolecular Chemistry; 11; 32; 18-6-2013; 5300-5309
1477-0520
url http://hdl.handle.net/11336/2178
identifier_str_mv Vignoni, Mariana; Rasse Suriani, Federico Ariel Osvaldo; Butzbach, Kathrin; Erra Balsells, Rosa; Epe, Bernd; et al.; Mechanisms of DNA damage by photoexcited 9-methyl-β-carbolines; Royal Society of Chemistry; Organic & Biomolecular Chemistry; 11; 32; 18-6-2013; 5300-5309
1477-0520
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://pubs.rsc.org/en/Content/ArticleLanding/2013/OB/c3ob40344k#!divAbstract
info:eu-repo/semantics/altIdentifier/doi/DOI:10.1039/C3OB40344K
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
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 12.48226

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