N-cinnamoylation of antimalarial classics: Quinacrine analogues with decreased toxicity and dual-stage activity
Autor(a) principal: | |
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Data de Publicação: | 2013 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://repositorio-aberto.up.pt/handle/10216/82163 |
Resumo: | Plasmodium falciparum, the causative agent of the most lethal form of malaria, is becoming increasingly resistant to most available drugs. A convenient approach to combat parasite resistance is the development of analogues of classical antimalarial agents, appropriately modified in order to restore their relevance in antimalarial chemotherapy. Following this line of thought, the design, synthesis and in vitro evaluation of N-cinnamoylated quinacrine surrogates, 9-(N-cinnamoylaminobutyl)-amino-6-chloro-2-methoxyacridines, is reported. The compounds were found to be highly potent against both blood-stage P.falciparum, chloroquine-sensitive 3D7 (IC50=17.0-39.0nM) and chloroquine-resistant W2 and Dd2 strains (IC50=3.2-41.2 and 27.1-131.0nM, respectively), and liver-stage P.berghei (IC50=1.6-4.9M) parasites. These findings bring new hope for the possible future "rise of a fallen angel" in antimalarial chemotherapy, with a potential resurgence of quinacrine-related compounds as dual-stage antimalarial leads. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
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N-cinnamoylation of antimalarial classics: Quinacrine analogues with decreased toxicity and dual-stage activityQuímicaChemical sciencesPlasmodium falciparum, the causative agent of the most lethal form of malaria, is becoming increasingly resistant to most available drugs. A convenient approach to combat parasite resistance is the development of analogues of classical antimalarial agents, appropriately modified in order to restore their relevance in antimalarial chemotherapy. Following this line of thought, the design, synthesis and in vitro evaluation of N-cinnamoylated quinacrine surrogates, 9-(N-cinnamoylaminobutyl)-amino-6-chloro-2-methoxyacridines, is reported. The compounds were found to be highly potent against both blood-stage P.falciparum, chloroquine-sensitive 3D7 (IC50=17.0-39.0nM) and chloroquine-resistant W2 and Dd2 strains (IC50=3.2-41.2 and 27.1-131.0nM, respectively), and liver-stage P.berghei (IC50=1.6-4.9M) parasites. These findings bring new hope for the possible future "rise of a fallen angel" in antimalarial chemotherapy, with a potential resurgence of quinacrine-related compounds as dual-stage antimalarial leads. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.20132013-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://repositorio-aberto.up.pt/handle/10216/82163eng1860-717910.1002/cmdc.201300459Gomes, APerez, BAlbuquerque, IMachado, MPrudencio, MNogueira, FTeixeira, CGomes, Pinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-29T16:05:55Zoai:repositorio-aberto.up.pt:10216/82163Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T00:37:47.388305Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
N-cinnamoylation of antimalarial classics: Quinacrine analogues with decreased toxicity and dual-stage activity |
title |
N-cinnamoylation of antimalarial classics: Quinacrine analogues with decreased toxicity and dual-stage activity |
spellingShingle |
N-cinnamoylation of antimalarial classics: Quinacrine analogues with decreased toxicity and dual-stage activity Gomes, A Química Chemical sciences |
title_short |
N-cinnamoylation of antimalarial classics: Quinacrine analogues with decreased toxicity and dual-stage activity |
title_full |
N-cinnamoylation of antimalarial classics: Quinacrine analogues with decreased toxicity and dual-stage activity |
title_fullStr |
N-cinnamoylation of antimalarial classics: Quinacrine analogues with decreased toxicity and dual-stage activity |
title_full_unstemmed |
N-cinnamoylation of antimalarial classics: Quinacrine analogues with decreased toxicity and dual-stage activity |
title_sort |
N-cinnamoylation of antimalarial classics: Quinacrine analogues with decreased toxicity and dual-stage activity |
author |
Gomes, A |
author_facet |
Gomes, A Perez, B Albuquerque, I Machado, M Prudencio, M Nogueira, F Teixeira, C Gomes, P |
author_role |
author |
author2 |
Perez, B Albuquerque, I Machado, M Prudencio, M Nogueira, F Teixeira, C Gomes, P |
author2_role |
author author author author author author author |
dc.contributor.author.fl_str_mv |
Gomes, A Perez, B Albuquerque, I Machado, M Prudencio, M Nogueira, F Teixeira, C Gomes, P |
dc.subject.por.fl_str_mv |
Química Chemical sciences |
topic |
Química Chemical sciences |
description |
Plasmodium falciparum, the causative agent of the most lethal form of malaria, is becoming increasingly resistant to most available drugs. A convenient approach to combat parasite resistance is the development of analogues of classical antimalarial agents, appropriately modified in order to restore their relevance in antimalarial chemotherapy. Following this line of thought, the design, synthesis and in vitro evaluation of N-cinnamoylated quinacrine surrogates, 9-(N-cinnamoylaminobutyl)-amino-6-chloro-2-methoxyacridines, is reported. The compounds were found to be highly potent against both blood-stage P.falciparum, chloroquine-sensitive 3D7 (IC50=17.0-39.0nM) and chloroquine-resistant W2 and Dd2 strains (IC50=3.2-41.2 and 27.1-131.0nM, respectively), and liver-stage P.berghei (IC50=1.6-4.9M) parasites. These findings bring new hope for the possible future "rise of a fallen angel" in antimalarial chemotherapy, with a potential resurgence of quinacrine-related compounds as dual-stage antimalarial leads. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013 2013-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://repositorio-aberto.up.pt/handle/10216/82163 |
url |
https://repositorio-aberto.up.pt/handle/10216/82163 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1860-7179 10.1002/cmdc.201300459 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799136285298786305 |