Evaluation of antimalarial activity and toxicity of a new primaquine prodrug
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2014 |
| Outros Autores: | , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/9722 |
Resumo: | Universidade Estadual Paulista. Faculdade de Ciencias Farmaceuticas. Departamento de Princıpios Ativos Naturais e Toxicologia. Araraquara, SP, Brazil |
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Davanço, Marcelo GomesAguiar, Anna Caroline CamposSantos, Leandro Alves dosPadilha, Elias CarvalhoCampos, Michel LeandroAndrade, Cleverton Roberto deFonseca, Luiz Marcos daSantos, Jean Leandro dosChin, Chung ManKrettli, Antoniana UrsinePeccinini, Rosangela Gonçalves2015-03-17T16:18:26Z2015-03-17T16:18:26Z2014DAVANÇO, Marcelo Gomes. Evaluation of antimalarial activity and toxicity of a new primaquine prodrug. PLoS ONE, v. 9, n. 8, p. e105217. 2014.1932-6203https://www.arca.fiocruz.br/handle/icict/972210.1371/journal.pone.0105217engPublic Library of ScienceEvaluation of antimalarial activity and toxicity of a new primaquine prodruginfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Estadual Paulista. Faculdade de Ciencias Farmaceuticas. Departamento de Princıpios Ativos Naturais e Toxicologia. Araraquara, SP, BrazilFundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, BrazilUniversidade Estadual Paulista. Faculdade de Odontologia de Araraquara. Departamento de Fisiologia e Patologia. Araraquara, SP, BrazilUniversidade Estadual Paulista. Faculdade de Ciencias Farmaceuticas. Departamento de Princıpios Ativos Naturais e Toxicologia. Araraquara, SP, BrazilUniversidade Estadual Paulista. Faculdade de Ciencias Farmaceuticas. Departamento de Princıpios Ativos Naturais e Toxicologia. Araraquara, SP, BrazilUniversidade Estadual Paulista. Faculdade de Odontologia de Araraquara. Departamento de Fisiologia e Patologia. Araraquara, SP, BrazilUniversidade Estadual Paulista. Faculdade de Ciencias Farmaceuticas. Departamento de Analises Clınicas. Araraquara, SP, BrazilUniversidade Estadual Paulista. Faculdade de Ciencias Farmaceuticas. Laboratorio de Pesquisa e Desenvolvimento de Farmacos. Araraquara, SP, BrazilUniversidade Estadual Paulista. Faculdade de Ciencias Farmaceuticas. Laboratorio de Pesquisa e Desenvolvimento de Farmacos. Araraquara, SP, BrazilFundação Oswaldo Cruz. Centro de Pesquisas Rene Rachou. Belo Horizonte, MG, BrazilUniversidade Estadual Paulista. Faculdade de Ciencias Farmaceuticas. Departamento de Princıpios Ativos Naturais e Toxicologia. Araraquara, SP, BrazilPlasmodium vivax is the most prevalent of the five species causing malaria in humans. The current available treatment for P. vivax malaria is limited and unsatisfactory due to at least two drawbacks: the undesirable side effects of primaquine (PQ) and drug resistance to chloroquine. Phenylalanine-alanine-PQ (Phe-Ala-PQ) is a PQ prodrug with a more favorable pharmacokinetic profile compared to PQ. The toxicity of this prodrug was evaluated in in vitro assays using a human hepatoma cell line (HepG2), a monkey kidney cell line (BGM), and human red blood cells deficient in the enzyme glucose-6-phosphate-dehydrogenase (G6PD). In addition, in vivo toxicity assays were performed with rats that received multiple doses of Phe-Ala-PQ to evaluate biochemical, hematological, and histopathological parameters. The activity was assessed by the inhibition of the sporogonic cycle using a chicken malaria parasite. Phe-Ala-PQ blocked malaria transmission in Aedes mosquitoes. When compared with PQ, it was less cytotoxic to BGM and HepG2 cells and caused less hemolysis of G6PD-deficient red blood cells at similar concentrations. The prodrug caused less alteration in the biochemical parameters than did PQ. Histopathological analysis of the liver and kidney did show differences between the control and Phe-Ala-PQ-treated groups, but they were not statistically significant. Taken together, the results highlight the prodrug as a novel lead compound candidate for the treatment of P. vivax malaria and as a blocker of malaria transmissionPlasmodium vivaxmalaria diseasesinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82352https://www.arca.fiocruz.br/bitstream/icict/9722/1/license.txtafbdf7d7a9bcf771a1cc7edf5f618413MD51ORIGINAL2014_153.pdf2014_153.pdfapplication/pdf799858https://www.arca.fiocruz.br/bitstream/icict/9722/2/2014_153.pdfd1be8c07fb4f88f06503b9b92110110aMD52TEXT2014_153.pdf.txt2014_153.pdf.txtExtracted texttext/plain47763https://www.arca.fiocruz.br/bitstream/icict/9722/3/2014_153.pdf.txta8ff63e164751faeb2b9595c6cf2aa2dMD53icict/97222019-06-19 10:07:34.655oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352019-06-19T13:07:34Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
| dc.title.pt_BR.fl_str_mv |
Evaluation of antimalarial activity and toxicity of a new primaquine prodrug |
| title |
Evaluation of antimalarial activity and toxicity of a new primaquine prodrug |
| spellingShingle |
Evaluation of antimalarial activity and toxicity of a new primaquine prodrug Davanço, Marcelo Gomes Plasmodium vivax malaria diseases |
| title_short |
Evaluation of antimalarial activity and toxicity of a new primaquine prodrug |
| title_full |
Evaluation of antimalarial activity and toxicity of a new primaquine prodrug |
| title_fullStr |
Evaluation of antimalarial activity and toxicity of a new primaquine prodrug |
| title_full_unstemmed |
Evaluation of antimalarial activity and toxicity of a new primaquine prodrug |
| title_sort |
Evaluation of antimalarial activity and toxicity of a new primaquine prodrug |
| author |
Davanço, Marcelo Gomes |
| author_facet |
Davanço, Marcelo Gomes Aguiar, Anna Caroline Campos Santos, Leandro Alves dos Padilha, Elias Carvalho Campos, Michel Leandro Andrade, Cleverton Roberto de Fonseca, Luiz Marcos da Santos, Jean Leandro dos Chin, Chung Man Krettli, Antoniana Ursine Peccinini, Rosangela Gonçalves |
| author_role |
author |
| author2 |
Aguiar, Anna Caroline Campos Santos, Leandro Alves dos Padilha, Elias Carvalho Campos, Michel Leandro Andrade, Cleverton Roberto de Fonseca, Luiz Marcos da Santos, Jean Leandro dos Chin, Chung Man Krettli, Antoniana Ursine Peccinini, Rosangela Gonçalves |
| author2_role |
author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Davanço, Marcelo Gomes Aguiar, Anna Caroline Campos Santos, Leandro Alves dos Padilha, Elias Carvalho Campos, Michel Leandro Andrade, Cleverton Roberto de Fonseca, Luiz Marcos da Santos, Jean Leandro dos Chin, Chung Man Krettli, Antoniana Ursine Peccinini, Rosangela Gonçalves |
| dc.subject.en.pt_BR.fl_str_mv |
Plasmodium vivax malaria diseases |
| topic |
Plasmodium vivax malaria diseases |
| description |
Universidade Estadual Paulista. Faculdade de Ciencias Farmaceuticas. Departamento de Princıpios Ativos Naturais e Toxicologia. Araraquara, SP, Brazil |
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2014 |
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2014 |
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2015-03-17T16:18:26Z |
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2015-03-17T16:18:26Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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DAVANÇO, Marcelo Gomes. Evaluation of antimalarial activity and toxicity of a new primaquine prodrug. PLoS ONE, v. 9, n. 8, p. e105217. 2014. |
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https://www.arca.fiocruz.br/handle/icict/9722 |
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1932-6203 |
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10.1371/journal.pone.0105217 |
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DAVANÇO, Marcelo Gomes. Evaluation of antimalarial activity and toxicity of a new primaquine prodrug. PLoS ONE, v. 9, n. 8, p. e105217. 2014. 1932-6203 10.1371/journal.pone.0105217 |
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