Antimalarial activity of new acridinone derivatives

Autores
Fernández Calienes, Aymé; Pellón, Rolando; Docampo, Maite; Fascio, Mirta Liliana; D'accorso, Norma Beatriz; Maes, Louis; Mendiola, Judith; Monzote, Lianet; Gille, Lars; Rojas, Lázara
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Malaria is one of the major threats concerning world public health. Resistance to the current antimalarial drugs has led to searches for new antimalarial compounds. Acridinone derivatives have recently demonstrated to be active against malaria parasite. We focused our attention on synthesized new acridinone derivatives, some of them resulting with high antiviral and trypanocidal activity. In this study new derivatives of 10-alyl-, 10-(3-methyl-2-butenyl)- and 10-(1,2-propadienyl)-9(10H)-acridinone were evaluated for their antimalarial activity against Plasmodium falciparum. To assess the selectivity, cytotoxicity was assessed in parallel against human MRC-5 cells. Inhibition of β-hematin formation was determined using a spectrophotometric assay. Mitochondrial bc 1 complexes were isolated from yeast and bovine heart cells to test acridinone inhibitory activity. This study resulted in the identification of three compounds with submicromolar efficacy against P. falciparum and without cytotoxic effects on human cellular line. One compound, IIa (1-fluoro-10-(3-methyl-2-butenyl)-9(10H)-acridinone), can be classified as hit for antimalarial drug development exhibiting IC 50 less than 0.2μg/mL with SI greater than 100. In molecular tests, no relevant inhibitory activity was obtained for our compounds. The mechanism of acridinones antimalarial action remains unclear.
Fil: Fernández Calienes, Aymé. Instituto de Medicina Tropical "Pedro Kourí"; Cuba
Fil: Pellón, Rolando. Universidad de La Habana; Cuba
Fil: Docampo, Maite. Universidad de La Habana; Cuba
Fil: Fascio, Mirta Liliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina
Fil: D'accorso, Norma Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina
Fil: Maes, Louis. Universiteit Antwerp; Bélgica
Fil: Mendiola, Judith. Instituto de Medicina Tropical "Pedro Kourí"; Cuba
Fil: Monzote, Lianet. Instituto de Medicina Tropical "Pedro Kourí"; Cuba
Fil: Gille, Lars. University of Veterinary Medicine; Austria
Fil: Rojas, Lázara. Instituto de Medicina Tropical "Pedro Kourí"; Cuba
Materia
ACRIDINONE
ANTIMALARIAL ACTIVITY
PLASMODIUM FALCIPARUM
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/68842
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/68842
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Antimalarial activity of new acridinone derivativesFernández Calienes, AyméPellón, RolandoDocampo, MaiteFascio, Mirta LilianaD'accorso, Norma BeatrizMaes, LouisMendiola, JudithMonzote, LianetGille, LarsRojas, LázaraACRIDINONEANTIMALARIAL ACTIVITYPLASMODIUM FALCIPARUMhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Malaria is one of the major threats concerning world public health. Resistance to the current antimalarial drugs has led to searches for new antimalarial compounds. Acridinone derivatives have recently demonstrated to be active against malaria parasite. We focused our attention on synthesized new acridinone derivatives, some of them resulting with high antiviral and trypanocidal activity. In this study new derivatives of 10-alyl-, 10-(3-methyl-2-butenyl)- and 10-(1,2-propadienyl)-9(10H)-acridinone were evaluated for their antimalarial activity against Plasmodium falciparum. To assess the selectivity, cytotoxicity was assessed in parallel against human MRC-5 cells. Inhibition of β-hematin formation was determined using a spectrophotometric assay. Mitochondrial bc 1 complexes were isolated from yeast and bovine heart cells to test acridinone inhibitory activity. This study resulted in the identification of three compounds with submicromolar efficacy against P. falciparum and without cytotoxic effects on human cellular line. One compound, IIa (1-fluoro-10-(3-methyl-2-butenyl)-9(10H)-acridinone), can be classified as hit for antimalarial drug development exhibiting IC 50 less than 0.2μg/mL with SI greater than 100. In molecular tests, no relevant inhibitory activity was obtained for our compounds. The mechanism of acridinones antimalarial action remains unclear.Fil: Fernández Calienes, Aymé. Instituto de Medicina Tropical "Pedro Kourí"; CubaFil: Pellón, Rolando. Universidad de La Habana; CubaFil: Docampo, Maite. Universidad de La Habana; CubaFil: Fascio, Mirta Liliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; ArgentinaFil: D'accorso, Norma Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; ArgentinaFil: Maes, Louis. Universiteit Antwerp; BélgicaFil: Mendiola, Judith. Instituto de Medicina Tropical "Pedro Kourí"; CubaFil: Monzote, Lianet. Instituto de Medicina Tropical "Pedro Kourí"; CubaFil: Gille, Lars. University of Veterinary Medicine; AustriaFil: Rojas, Lázara. Instituto de Medicina Tropical "Pedro Kourí"; CubaElsevier Masson2011-06info: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/11336/68842Fernández Calienes, Aymé; Pellón, Rolando; Docampo, Maite; Fascio, Mirta Liliana; D'accorso, Norma Beatriz; et al.; Antimalarial activity of new acridinone derivatives; Elsevier Masson; Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie; 65; 3; 6-2011; 210-2140753-3322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.biopha.2011.04.001info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0753332211000217info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:28:54Zoai:ri.conicet.gov.ar:11336/68842instacron: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 10:28:54.678CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Antimalarial activity of new acridinone derivatives
title Antimalarial activity of new acridinone derivatives
spellingShingle Antimalarial activity of new acridinone derivatives
Fernández Calienes, Aymé
ACRIDINONE
ANTIMALARIAL ACTIVITY
PLASMODIUM FALCIPARUM
title_short Antimalarial activity of new acridinone derivatives
title_full Antimalarial activity of new acridinone derivatives
title_fullStr Antimalarial activity of new acridinone derivatives
title_full_unstemmed Antimalarial activity of new acridinone derivatives
title_sort Antimalarial activity of new acridinone derivatives
dc.creator.none.fl_str_mv Fernández Calienes, Aymé
Pellón, Rolando
Docampo, Maite
Fascio, Mirta Liliana
D'accorso, Norma Beatriz
Maes, Louis
Mendiola, Judith
Monzote, Lianet
Gille, Lars
Rojas, Lázara
author Fernández Calienes, Aymé
author_facet Fernández Calienes, Aymé
Pellón, Rolando
Docampo, Maite
Fascio, Mirta Liliana
D'accorso, Norma Beatriz
Maes, Louis
Mendiola, Judith
Monzote, Lianet
Gille, Lars
Rojas, Lázara
author_role author
author2 Pellón, Rolando
Docampo, Maite
Fascio, Mirta Liliana
D'accorso, Norma Beatriz
Maes, Louis
Mendiola, Judith
Monzote, Lianet
Gille, Lars
Rojas, Lázara
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ACRIDINONE
ANTIMALARIAL ACTIVITY
PLASMODIUM FALCIPARUM
topic ACRIDINONE
ANTIMALARIAL ACTIVITY
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 Malaria is one of the major threats concerning world public health. Resistance to the current antimalarial drugs has led to searches for new antimalarial compounds. Acridinone derivatives have recently demonstrated to be active against malaria parasite. We focused our attention on synthesized new acridinone derivatives, some of them resulting with high antiviral and trypanocidal activity. In this study new derivatives of 10-alyl-, 10-(3-methyl-2-butenyl)- and 10-(1,2-propadienyl)-9(10H)-acridinone were evaluated for their antimalarial activity against Plasmodium falciparum. To assess the selectivity, cytotoxicity was assessed in parallel against human MRC-5 cells. Inhibition of β-hematin formation was determined using a spectrophotometric assay. Mitochondrial bc 1 complexes were isolated from yeast and bovine heart cells to test acridinone inhibitory activity. This study resulted in the identification of three compounds with submicromolar efficacy against P. falciparum and without cytotoxic effects on human cellular line. One compound, IIa (1-fluoro-10-(3-methyl-2-butenyl)-9(10H)-acridinone), can be classified as hit for antimalarial drug development exhibiting IC 50 less than 0.2μg/mL with SI greater than 100. In molecular tests, no relevant inhibitory activity was obtained for our compounds. The mechanism of acridinones antimalarial action remains unclear.
Fil: Fernández Calienes, Aymé. Instituto de Medicina Tropical "Pedro Kourí"; Cuba
Fil: Pellón, Rolando. Universidad de La Habana; Cuba
Fil: Docampo, Maite. Universidad de La Habana; Cuba
Fil: Fascio, Mirta Liliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina
Fil: D'accorso, Norma Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina
Fil: Maes, Louis. Universiteit Antwerp; Bélgica
Fil: Mendiola, Judith. Instituto de Medicina Tropical "Pedro Kourí"; Cuba
Fil: Monzote, Lianet. Instituto de Medicina Tropical "Pedro Kourí"; Cuba
Fil: Gille, Lars. University of Veterinary Medicine; Austria
Fil: Rojas, Lázara. Instituto de Medicina Tropical "Pedro Kourí"; Cuba
description Malaria is one of the major threats concerning world public health. Resistance to the current antimalarial drugs has led to searches for new antimalarial compounds. Acridinone derivatives have recently demonstrated to be active against malaria parasite. We focused our attention on synthesized new acridinone derivatives, some of them resulting with high antiviral and trypanocidal activity. In this study new derivatives of 10-alyl-, 10-(3-methyl-2-butenyl)- and 10-(1,2-propadienyl)-9(10H)-acridinone were evaluated for their antimalarial activity against Plasmodium falciparum. To assess the selectivity, cytotoxicity was assessed in parallel against human MRC-5 cells. Inhibition of β-hematin formation was determined using a spectrophotometric assay. Mitochondrial bc 1 complexes were isolated from yeast and bovine heart cells to test acridinone inhibitory activity. This study resulted in the identification of three compounds with submicromolar efficacy against P. falciparum and without cytotoxic effects on human cellular line. One compound, IIa (1-fluoro-10-(3-methyl-2-butenyl)-9(10H)-acridinone), can be classified as hit for antimalarial drug development exhibiting IC 50 less than 0.2μg/mL with SI greater than 100. In molecular tests, no relevant inhibitory activity was obtained for our compounds. The mechanism of acridinones antimalarial action remains unclear.
publishDate 2011
dc.date.none.fl_str_mv 2011-06
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/11336/68842
Fernández Calienes, Aymé; Pellón, Rolando; Docampo, Maite; Fascio, Mirta Liliana; D'accorso, Norma Beatriz; et al.; Antimalarial activity of new acridinone derivatives; Elsevier Masson; Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie; 65; 3; 6-2011; 210-214
0753-3322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/68842
identifier_str_mv Fernández Calienes, Aymé; Pellón, Rolando; Docampo, Maite; Fascio, Mirta Liliana; D'accorso, Norma Beatriz; et al.; Antimalarial activity of new acridinone derivatives; Elsevier Masson; Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie; 65; 3; 6-2011; 210-214
0753-3322
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.biopha.2011.04.001
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0753332211000217
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Masson
publisher.none.fl_str_mv Elsevier Masson
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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