Imidazoquines as Antimalarial and Antipneumocystis Agents
Autor(a) principal: | |
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Data de Publicação: | 2009 |
Outros Autores: | , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | https://hdl.handle.net/10216/82100 |
Resumo: | Peptidomimetic imidazolidin-4-one derivatives of primaquine (imidazoquines) recently displayed in vitro activity against blood schizonts of a chloroquine-resistant strain of Plasmodium falciparum. Preliminary studies with a subset of such imidazoquines showed them to both block transmission of P. berghei malaria front mouse to mosquito and be highly stable toward hydrolysis at physiological conditions. This prompted Lis to have deeper insight into the activity of imidazoquines against both Plasmodia and Pneumocystis carinii, on which primaquine is also active. Full assessment of the in vivo transmission-blocking activity of imidazoquines, in vitro tissue-schizontocidal activity on P. berghei-infected hepatocytes, and in vitro anti-P. carinii activity is now reported. All compounds were active in these biological assays, with generally lower activity than the parent drug. However, imidazoquines' stability against both oxidative deamination and proteolytic degradation suggest that they will probably have higher oral bioavailability and lower hematotoxicity than primaquine, which might translate into higher therapeutic indexes. |
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Imidazoquines as Antimalarial and Antipneumocystis AgentsMedicina básicaBasic medicinePeptidomimetic imidazolidin-4-one derivatives of primaquine (imidazoquines) recently displayed in vitro activity against blood schizonts of a chloroquine-resistant strain of Plasmodium falciparum. Preliminary studies with a subset of such imidazoquines showed them to both block transmission of P. berghei malaria front mouse to mosquito and be highly stable toward hydrolysis at physiological conditions. This prompted Lis to have deeper insight into the activity of imidazoquines against both Plasmodia and Pneumocystis carinii, on which primaquine is also active. Full assessment of the in vivo transmission-blocking activity of imidazoquines, in vitro tissue-schizontocidal activity on P. berghei-infected hepatocytes, and in vitro anti-P. carinii activity is now reported. All compounds were active in these biological assays, with generally lower activity than the parent drug. However, imidazoquines' stability against both oxidative deamination and proteolytic degradation suggest that they will probably have higher oral bioavailability and lower hematotoxicity than primaquine, which might translate into higher therapeutic indexes.20092009-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10216/82100eng0022-262310.1021/jm900738cNuno ValeMiguel PrudencioCatarina A MarquesMargaret S CollinsJiri GutFatima NogueiraJoana MatosPhilip J RosenthalMelanie T CushionVirgilio E do RosarioMaria M MotaRui MoreiraPaula Gomesinfo: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:RCAAP2023-11-29T14:45:56Zoai:repositorio-aberto.up.pt:10216/82100Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T00:08:00.537755Repositório 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 |
Imidazoquines as Antimalarial and Antipneumocystis Agents |
title |
Imidazoquines as Antimalarial and Antipneumocystis Agents |
spellingShingle |
Imidazoquines as Antimalarial and Antipneumocystis Agents Nuno Vale Medicina básica Basic medicine |
title_short |
Imidazoquines as Antimalarial and Antipneumocystis Agents |
title_full |
Imidazoquines as Antimalarial and Antipneumocystis Agents |
title_fullStr |
Imidazoquines as Antimalarial and Antipneumocystis Agents |
title_full_unstemmed |
Imidazoquines as Antimalarial and Antipneumocystis Agents |
title_sort |
Imidazoquines as Antimalarial and Antipneumocystis Agents |
author |
Nuno Vale |
author_facet |
Nuno Vale Miguel Prudencio Catarina A Marques Margaret S Collins Jiri Gut Fatima Nogueira Joana Matos Philip J Rosenthal Melanie T Cushion Virgilio E do Rosario Maria M Mota Rui Moreira Paula Gomes |
author_role |
author |
author2 |
Miguel Prudencio Catarina A Marques Margaret S Collins Jiri Gut Fatima Nogueira Joana Matos Philip J Rosenthal Melanie T Cushion Virgilio E do Rosario Maria M Mota Rui Moreira Paula Gomes |
author2_role |
author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Nuno Vale Miguel Prudencio Catarina A Marques Margaret S Collins Jiri Gut Fatima Nogueira Joana Matos Philip J Rosenthal Melanie T Cushion Virgilio E do Rosario Maria M Mota Rui Moreira Paula Gomes |
dc.subject.por.fl_str_mv |
Medicina básica Basic medicine |
topic |
Medicina básica Basic medicine |
description |
Peptidomimetic imidazolidin-4-one derivatives of primaquine (imidazoquines) recently displayed in vitro activity against blood schizonts of a chloroquine-resistant strain of Plasmodium falciparum. Preliminary studies with a subset of such imidazoquines showed them to both block transmission of P. berghei malaria front mouse to mosquito and be highly stable toward hydrolysis at physiological conditions. This prompted Lis to have deeper insight into the activity of imidazoquines against both Plasmodia and Pneumocystis carinii, on which primaquine is also active. Full assessment of the in vivo transmission-blocking activity of imidazoquines, in vitro tissue-schizontocidal activity on P. berghei-infected hepatocytes, and in vitro anti-P. carinii activity is now reported. All compounds were active in these biological assays, with generally lower activity than the parent drug. However, imidazoquines' stability against both oxidative deamination and proteolytic degradation suggest that they will probably have higher oral bioavailability and lower hematotoxicity than primaquine, which might translate into higher therapeutic indexes. |
publishDate |
2009 |
dc.date.none.fl_str_mv |
2009 2009-01-01T00:00:00Z |
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://hdl.handle.net/10216/82100 |
url |
https://hdl.handle.net/10216/82100 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0022-2623 10.1021/jm900738c |
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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