Antimalarial activity of novel imidazoisoquinolinone derivatives correlates with heme binding affinity

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 betw...

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Autores: Bollini, Mariela, Casal, Juan José, Asís, Silvia Elizabeth, Leal, Emilse Soledad, Bruno, Ana María
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:Argentina
Recursos:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/38723
Acesso em linha:http://hdl.handle.net/11336/38723
Access Level:acceso abierto
Palavra-chave:Antiplasmodial
Hemozoin
Imidazoisoquinolinones
Malaria
Plasmodium Falciparum
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
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network_name_str Argentina
repository_id_str
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 Técnicas2024-05-08T14:13:30Zoai: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:34982024-05-08 14:13:31.279CONICET 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
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
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
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
topic Antiplasmodial
Hemozoin
Imidazoisoquinolinones
Malaria
Plasmodium Falciparum
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
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
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
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
_version_ 1799196065961869312
score 15,812429

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