Antimalarial activity of novel imidazoisoquinolinone derivatives correlates with heme binding affinity

Autores
Bollini, Mariela; Casal, Juan José; Asís, Silvia Elizabeth; Leal, Emilse Soledad; Bruno, Ana María
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
A series of novel imidazoisoquinolinone derivatives were synthesized and evaluated for in vitro antimalarial efficacy against chloroquine sensitive GHA strain of Plasmodium falciparum. Compounds 2, 4, 6, 9, and 17 revealed moderate to good activities in the micromolar range. Binding interaction between these active compounds and heme were determined and correlated with antimalarial activity. A good correlation (r = 0.98) was observed between antimalarial activity and the heme dissociation constants (K d). These suggest that antimalarial mode of action of this class of compounds appears to be similar to that of chloroquine and involves the inhibition of hemozoin formation.
Fil: Bollini, Mariela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Casal, Juan José. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Asís, Silvia Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina
Fil: Leal, Emilse Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina
Fil: Bruno, Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina
Materia
Antiplasmodial
Hemozoin
Imidazoisoquinolinones
Malaria
Plasmodium Falciparum
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:11336/38723
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Antimalarial activity of novel imidazoisoquinolinone derivatives correlates with heme binding affinityBollini, MarielaCasal, Juan JoséAsís, Silvia ElizabethLeal, Emilse SoledadBruno, Ana MaríaAntiplasmodialHemozoinImidazoisoquinolinonesMalariaPlasmodium Falciparumhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1A series of novel imidazoisoquinolinone derivatives were synthesized and evaluated for in vitro antimalarial efficacy against chloroquine sensitive GHA strain of Plasmodium falciparum. Compounds 2, 4, 6, 9, and 17 revealed moderate to good activities in the micromolar range. Binding interaction between these active compounds and heme were determined and correlated with antimalarial activity. A good correlation (r = 0.98) was observed between antimalarial activity and the heme dissociation constants (K d). These suggest that antimalarial mode of action of this class of compounds appears to be similar to that of chloroquine and involves the inhibition of hemozoin formation.Fil: Bollini, Mariela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Casal, Juan José. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Asís, Silvia Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; ArgentinaFil: Leal, Emilse Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; ArgentinaFil: Bruno, Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; ArgentinaBirkhauser Boston Inc2015-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/38723Bollini, Mariela; Casal, Juan José; Asís, Silvia Elizabeth; Leal, Emilse Soledad; Bruno, Ana María; Antimalarial activity of novel imidazoisoquinolinone derivatives correlates with heme binding affinity; Birkhauser Boston Inc; Medicinal Chemistry Research; 24; 4; 3-2015; 1496-15031054-2523CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1007/s00044-014-1231-6info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs00044-014-1231-6info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:26:38Zoai:ri.conicet.gov.ar:11336/38723instacron: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:34982025-09-29 10:26:39.179CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Antimalarial activity of novel imidazoisoquinolinone derivatives correlates with heme binding affinity
title Antimalarial activity of novel imidazoisoquinolinone derivatives correlates with heme binding affinity
spellingShingle Antimalarial activity of novel imidazoisoquinolinone derivatives correlates with heme binding affinity
Bollini, Mariela
Antiplasmodial
Hemozoin
Imidazoisoquinolinones
Malaria
Plasmodium Falciparum
title_short Antimalarial activity of novel imidazoisoquinolinone derivatives correlates with heme binding affinity
title_full Antimalarial activity of novel imidazoisoquinolinone derivatives correlates with heme binding affinity
title_fullStr Antimalarial activity of novel imidazoisoquinolinone derivatives correlates with heme binding affinity
title_full_unstemmed Antimalarial activity of novel imidazoisoquinolinone derivatives correlates with heme binding affinity
title_sort Antimalarial activity of novel imidazoisoquinolinone derivatives correlates with heme binding affinity
dc.creator.none.fl_str_mv Bollini, Mariela
Casal, Juan José
Asís, Silvia Elizabeth
Leal, Emilse Soledad
Bruno, Ana María
author Bollini, Mariela
author_facet Bollini, Mariela
Casal, Juan José
Asís, Silvia Elizabeth
Leal, Emilse Soledad
Bruno, Ana María
author_role author
author2 Casal, Juan José
Asís, Silvia Elizabeth
Leal, Emilse Soledad
Bruno, Ana María
author2_role author
author
author
author
dc.subject.none.fl_str_mv Antiplasmodial
Hemozoin
Imidazoisoquinolinones
Malaria
Plasmodium Falciparum
topic Antiplasmodial
Hemozoin
Imidazoisoquinolinones
Malaria
Plasmodium Falciparum
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv A series of novel imidazoisoquinolinone derivatives were synthesized and evaluated for in vitro antimalarial efficacy against chloroquine sensitive GHA strain of Plasmodium falciparum. Compounds 2, 4, 6, 9, and 17 revealed moderate to good activities in the micromolar range. Binding interaction between these active compounds and heme were determined and correlated with antimalarial activity. A good correlation (r = 0.98) was observed between antimalarial activity and the heme dissociation constants (K d). These suggest that antimalarial mode of action of this class of compounds appears to be similar to that of chloroquine and involves the inhibition of hemozoin formation.
Fil: Bollini, Mariela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Casal, Juan José. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina
Fil: Asís, Silvia Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina
Fil: Leal, Emilse Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina
Fil: Bruno, Ana María. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina
description A series of novel imidazoisoquinolinone derivatives were synthesized and evaluated for in vitro antimalarial efficacy against chloroquine sensitive GHA strain of Plasmodium falciparum. Compounds 2, 4, 6, 9, and 17 revealed moderate to good activities in the micromolar range. Binding interaction between these active compounds and heme were determined and correlated with antimalarial activity. A good correlation (r = 0.98) was observed between antimalarial activity and the heme dissociation constants (K d). These suggest that antimalarial mode of action of this class of compounds appears to be similar to that of chloroquine and involves the inhibition of hemozoin formation.
publishDate 2015
dc.date.none.fl_str_mv 2015-03
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/11336/38723
Bollini, Mariela; Casal, Juan José; Asís, Silvia Elizabeth; Leal, Emilse Soledad; Bruno, Ana María; Antimalarial activity of novel imidazoisoquinolinone derivatives correlates with heme binding affinity; Birkhauser Boston Inc; Medicinal Chemistry Research; 24; 4; 3-2015; 1496-1503
1054-2523
CONICET Digital
CONICET
url http://hdl.handle.net/11336/38723
identifier_str_mv Bollini, Mariela; Casal, Juan José; Asís, Silvia Elizabeth; Leal, Emilse Soledad; Bruno, Ana María; Antimalarial activity of novel imidazoisoquinolinone derivatives correlates with heme binding affinity; Birkhauser Boston Inc; Medicinal Chemistry Research; 24; 4; 3-2015; 1496-1503
1054-2523
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1007/s00044-014-1231-6
info:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs00044-014-1231-6
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.publisher.none.fl_str_mv Birkhauser Boston Inc
publisher.none.fl_str_mv Birkhauser Boston Inc
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 13.069144

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