Mechanism of action of novel naphthofuranquinones on rat liver microsomal peroxidation

Autores
Elingold, Igal; Taboas, Melisa Ivana; Casanova, Marta Beatriz; Galleano, Mónica Liliana; Silva, Raphael S.F.; Menna Barreto, Rubem F.S.; Ventura Pinto, Antonio; de Castro, Solange L.; Costa, Lidia Esther; Dubin, Marta
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In order to elucidate the effect on mammal systems of new derivatives from 2-hydroxy-3-allyl-naphthoquinone, á-iodinated naphthofuranquinone (NPPN-3223), â-iodinated naphthofuranquinone (NPPN-3222) and â-methyl naphthofuranquinone (NPPN-3226) synthesized as possible trypanocidal agents, their effect on rat liver microsomal lipid peroxidation was investigated. They (a) inhibited NADPH-dependent, iron-catalyzed microsomal rat liver lipid peroxidation; (b) did not inhibit the tert-butyl hydroperoxide-dependent lipid peroxidation; (c) did not inhibit ascorbate?lipid peroxidation with the exception of NPPN-3226 which did inhibit it; (d) stimulated NADPH oxidation and microsomal oxygen uptake; (e) increased superoxide anion formation by NADPH-supplemented microsomes and (f) stimulated ascorbate oxidation. The three drugs were reduced to their seminaphthofuranquinone radical by the liver NADPH?P450 reductase system, as detected by ESR measurements. These results support the hypothesis that naphthofuranquinones reduction by microsomal NADPH?P450 reductase and semiquinone oxidation by molecular oxygen diverts electrons, preventing microsomal lipid peroxidation. In addition, hydroquinones and/or semiquinones formed by naphthofuranquinones reduction would be capable of lipid peroxidation inhibition and on interacting with the lipid peroxide radicals can lead to an antioxidant effect as we suggested for NPPN-3226 in close agreement to the inhibition of ascorbate?lipid peroxidation. Due to the properties of these molecules and their incoming structure developments, naphthofuranquinones would be considered as potentially promising therapeutic agents, mainly against Chagas disease.
Fil: Elingold, Igal. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Taboas, Melisa Ivana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Casanova, Marta Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Galleano, Mónica Liliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Programa de Radicales Libres; Argentina
Fil: Silva, Raphael S.F.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Menna Barreto, Rubem F.S.. Fundación Oswaldo Cruz; Brasil
Fil: Ventura Pinto, Antonio. Universidade Federal do Rio de Janeiro; Brasil
Fil: de Castro, Solange L.. Fundación Oswaldo Cruz; Brasil
Fil: Costa, Lidia Esther. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Programa de Radicales Libres; Argentina
Fil: Dubin, Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Materia
NAPHTHOQUINONES
LIPID PEROXIDATION
CHAGAS DISEASE
NAPHTHOFURANQUINONES
OXIDATIVE STRESS
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:11336/102746
Acceder
id CONICETDig_de57bbf2bc62dfb775c6eb627c74a2cf
oai_identifier_str oai:ri.conicet.gov.ar:11336/102746
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Mechanism of action of novel naphthofuranquinones on rat liver microsomal peroxidationElingold, IgalTaboas, Melisa IvanaCasanova, Marta BeatrizGalleano, Mónica LilianaSilva, Raphael S.F.Menna Barreto, Rubem F.S.Ventura Pinto, Antoniode Castro, Solange L.Costa, Lidia EstherDubin, MartaNAPHTHOQUINONESLIPID PEROXIDATIONCHAGAS DISEASENAPHTHOFURANQUINONESOXIDATIVE STRESShttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3In order to elucidate the effect on mammal systems of new derivatives from 2-hydroxy-3-allyl-naphthoquinone, á-iodinated naphthofuranquinone (NPPN-3223), â-iodinated naphthofuranquinone (NPPN-3222) and â-methyl naphthofuranquinone (NPPN-3226) synthesized as possible trypanocidal agents, their effect on rat liver microsomal lipid peroxidation was investigated. They (a) inhibited NADPH-dependent, iron-catalyzed microsomal rat liver lipid peroxidation; (b) did not inhibit the tert-butyl hydroperoxide-dependent lipid peroxidation; (c) did not inhibit ascorbate?lipid peroxidation with the exception of NPPN-3226 which did inhibit it; (d) stimulated NADPH oxidation and microsomal oxygen uptake; (e) increased superoxide anion formation by NADPH-supplemented microsomes and (f) stimulated ascorbate oxidation. The three drugs were reduced to their seminaphthofuranquinone radical by the liver NADPH?P450 reductase system, as detected by ESR measurements. These results support the hypothesis that naphthofuranquinones reduction by microsomal NADPH?P450 reductase and semiquinone oxidation by molecular oxygen diverts electrons, preventing microsomal lipid peroxidation. In addition, hydroquinones and/or semiquinones formed by naphthofuranquinones reduction would be capable of lipid peroxidation inhibition and on interacting with the lipid peroxide radicals can lead to an antioxidant effect as we suggested for NPPN-3226 in close agreement to the inhibition of ascorbate?lipid peroxidation. Due to the properties of these molecules and their incoming structure developments, naphthofuranquinones would be considered as potentially promising therapeutic agents, mainly against Chagas disease.Fil: Elingold, Igal. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Taboas, Melisa Ivana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Casanova, Marta Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Galleano, Mónica Liliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Programa de Radicales Libres; ArgentinaFil: Silva, Raphael S.F.. Universidade Federal do Rio de Janeiro; BrasilFil: Menna Barreto, Rubem F.S.. Fundación Oswaldo Cruz; BrasilFil: Ventura Pinto, Antonio. Universidade Federal do Rio de Janeiro; BrasilFil: de Castro, Solange L.. Fundación Oswaldo Cruz; BrasilFil: Costa, Lidia Esther. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Programa de Radicales Libres; ArgentinaFil: Dubin, Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaElsevier Ireland2009-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/102746Elingold, Igal; Taboas, Melisa Ivana; Casanova, Marta Beatriz; Galleano, Mónica Liliana; Silva, Raphael S.F.; et al.; Mechanism of action of novel naphthofuranquinones on rat liver microsomal peroxidation; Elsevier Ireland; Chemico-biological Interactions; 182; 2-3; 12-2009; 213-2190009-2797CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0009279709003561info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cbi.2009.09.002info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:46:53Zoai:ri.conicet.gov.ar:11336/102746instacron: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 14:46:54.071CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Mechanism of action of novel naphthofuranquinones on rat liver microsomal peroxidation
title Mechanism of action of novel naphthofuranquinones on rat liver microsomal peroxidation
spellingShingle Mechanism of action of novel naphthofuranquinones on rat liver microsomal peroxidation
Elingold, Igal
NAPHTHOQUINONES
LIPID PEROXIDATION
CHAGAS DISEASE
NAPHTHOFURANQUINONES
OXIDATIVE STRESS
title_short Mechanism of action of novel naphthofuranquinones on rat liver microsomal peroxidation
title_full Mechanism of action of novel naphthofuranquinones on rat liver microsomal peroxidation
title_fullStr Mechanism of action of novel naphthofuranquinones on rat liver microsomal peroxidation
title_full_unstemmed Mechanism of action of novel naphthofuranquinones on rat liver microsomal peroxidation
title_sort Mechanism of action of novel naphthofuranquinones on rat liver microsomal peroxidation
dc.creator.none.fl_str_mv Elingold, Igal
Taboas, Melisa Ivana
Casanova, Marta Beatriz
Galleano, Mónica Liliana
Silva, Raphael S.F.
Menna Barreto, Rubem F.S.
Ventura Pinto, Antonio
de Castro, Solange L.
Costa, Lidia Esther
Dubin, Marta
author Elingold, Igal
author_facet Elingold, Igal
Taboas, Melisa Ivana
Casanova, Marta Beatriz
Galleano, Mónica Liliana
Silva, Raphael S.F.
Menna Barreto, Rubem F.S.
Ventura Pinto, Antonio
de Castro, Solange L.
Costa, Lidia Esther
Dubin, Marta
author_role author
author2 Taboas, Melisa Ivana
Casanova, Marta Beatriz
Galleano, Mónica Liliana
Silva, Raphael S.F.
Menna Barreto, Rubem F.S.
Ventura Pinto, Antonio
de Castro, Solange L.
Costa, Lidia Esther
Dubin, Marta
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv NAPHTHOQUINONES
LIPID PEROXIDATION
CHAGAS DISEASE
NAPHTHOFURANQUINONES
OXIDATIVE STRESS
topic NAPHTHOQUINONES
LIPID PEROXIDATION
CHAGAS DISEASE
NAPHTHOFURANQUINONES
OXIDATIVE STRESS
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv In order to elucidate the effect on mammal systems of new derivatives from 2-hydroxy-3-allyl-naphthoquinone, á-iodinated naphthofuranquinone (NPPN-3223), â-iodinated naphthofuranquinone (NPPN-3222) and â-methyl naphthofuranquinone (NPPN-3226) synthesized as possible trypanocidal agents, their effect on rat liver microsomal lipid peroxidation was investigated. They (a) inhibited NADPH-dependent, iron-catalyzed microsomal rat liver lipid peroxidation; (b) did not inhibit the tert-butyl hydroperoxide-dependent lipid peroxidation; (c) did not inhibit ascorbate?lipid peroxidation with the exception of NPPN-3226 which did inhibit it; (d) stimulated NADPH oxidation and microsomal oxygen uptake; (e) increased superoxide anion formation by NADPH-supplemented microsomes and (f) stimulated ascorbate oxidation. The three drugs were reduced to their seminaphthofuranquinone radical by the liver NADPH?P450 reductase system, as detected by ESR measurements. These results support the hypothesis that naphthofuranquinones reduction by microsomal NADPH?P450 reductase and semiquinone oxidation by molecular oxygen diverts electrons, preventing microsomal lipid peroxidation. In addition, hydroquinones and/or semiquinones formed by naphthofuranquinones reduction would be capable of lipid peroxidation inhibition and on interacting with the lipid peroxide radicals can lead to an antioxidant effect as we suggested for NPPN-3226 in close agreement to the inhibition of ascorbate?lipid peroxidation. Due to the properties of these molecules and their incoming structure developments, naphthofuranquinones would be considered as potentially promising therapeutic agents, mainly against Chagas disease.
Fil: Elingold, Igal. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Taboas, Melisa Ivana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Casanova, Marta Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
Fil: Galleano, Mónica Liliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Programa de Radicales Libres; Argentina
Fil: Silva, Raphael S.F.. Universidade Federal do Rio de Janeiro; Brasil
Fil: Menna Barreto, Rubem F.S.. Fundación Oswaldo Cruz; Brasil
Fil: Ventura Pinto, Antonio. Universidade Federal do Rio de Janeiro; Brasil
Fil: de Castro, Solange L.. Fundación Oswaldo Cruz; Brasil
Fil: Costa, Lidia Esther. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Cardiológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Programa de Radicales Libres; Argentina
Fil: Dubin, Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; Argentina
description In order to elucidate the effect on mammal systems of new derivatives from 2-hydroxy-3-allyl-naphthoquinone, á-iodinated naphthofuranquinone (NPPN-3223), â-iodinated naphthofuranquinone (NPPN-3222) and â-methyl naphthofuranquinone (NPPN-3226) synthesized as possible trypanocidal agents, their effect on rat liver microsomal lipid peroxidation was investigated. They (a) inhibited NADPH-dependent, iron-catalyzed microsomal rat liver lipid peroxidation; (b) did not inhibit the tert-butyl hydroperoxide-dependent lipid peroxidation; (c) did not inhibit ascorbate?lipid peroxidation with the exception of NPPN-3226 which did inhibit it; (d) stimulated NADPH oxidation and microsomal oxygen uptake; (e) increased superoxide anion formation by NADPH-supplemented microsomes and (f) stimulated ascorbate oxidation. The three drugs were reduced to their seminaphthofuranquinone radical by the liver NADPH?P450 reductase system, as detected by ESR measurements. These results support the hypothesis that naphthofuranquinones reduction by microsomal NADPH?P450 reductase and semiquinone oxidation by molecular oxygen diverts electrons, preventing microsomal lipid peroxidation. In addition, hydroquinones and/or semiquinones formed by naphthofuranquinones reduction would be capable of lipid peroxidation inhibition and on interacting with the lipid peroxide radicals can lead to an antioxidant effect as we suggested for NPPN-3226 in close agreement to the inhibition of ascorbate?lipid peroxidation. Due to the properties of these molecules and their incoming structure developments, naphthofuranquinones would be considered as potentially promising therapeutic agents, mainly against Chagas disease.
publishDate 2009
dc.date.none.fl_str_mv 2009-12
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/11336/102746
Elingold, Igal; Taboas, Melisa Ivana; Casanova, Marta Beatriz; Galleano, Mónica Liliana; Silva, Raphael S.F.; et al.; Mechanism of action of novel naphthofuranquinones on rat liver microsomal peroxidation; Elsevier Ireland; Chemico-biological Interactions; 182; 2-3; 12-2009; 213-219
0009-2797
CONICET Digital
CONICET
url http://hdl.handle.net/11336/102746
identifier_str_mv Elingold, Igal; Taboas, Melisa Ivana; Casanova, Marta Beatriz; Galleano, Mónica Liliana; Silva, Raphael S.F.; et al.; Mechanism of action of novel naphthofuranquinones on rat liver microsomal peroxidation; Elsevier Ireland; Chemico-biological Interactions; 182; 2-3; 12-2009; 213-219
0009-2797
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/abs/pii/S0009279709003561
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.cbi.2009.09.002
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
application/pdf
dc.publisher.none.fl_str_mv Elsevier Ireland
publisher.none.fl_str_mv Elsevier Ireland
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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