In Vivo Antimalarial Activity and Mechanisms of Action of 4-Nerolidylcatechol Derivatives
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2015 |
| 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/12568 |
Resumo: | Instituto Nacional Para Pesquisa da Amazonia. Manaus, AM, Brasil/Universidade Federal da Amazonas. Manaus, AM, Brasil/Universidade Centro Norte. Manaus, AM, Brasil |
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Silva, Luiz Francisco Rocha eNogueira, Karla LagosPinto, Ana Cristina da SilvaKatzin, Alejandro MiguelSussmann, Rodrigo A. C.Muniz, Magno PerêaNeto, Valter Ferreira de AndradeChaves, Francisco Célio MaiaCoutinho, Julia PennaLima, Emerson SilvaKrettli, Antoniana UrsineTadei, Wanderli PedroPohlit, Adrian Martin2016-01-20T14:46:14Z2016-01-20T14:46:14Z2015SILVA, Luiz Francisco Rocha e et al. In Vivo Antimalarial Activity and Mechanisms of Action of 4-Nerolidylcatechol Derivatives. Antimicrob Agents Chemother., vol. 59, n. 6, p. 3271–3280, 2015.1098-6596https://www.arca.fiocruz.br/handle/icict/1256810.1128/AAC.05012-14engAmerican Society for MicrobiologyIn Vivo Antimalarial Activity and Mechanisms of Action of 4-Nerolidylcatechol Derivativesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleInstituto Nacional Para Pesquisa da Amazonia. Manaus, AM, Brasil/Universidade Federal da Amazonas. Manaus, AM, Brasil/Universidade Centro Norte. Manaus, AM, BrasilInstituto Nacional Para Pesquisa da Amazonia. Manaus, AM, Brasil/Universidade Federal da Amazonas. Manaus, AM, BrasilInstituto Nacional Para Pesquisa da Amazonia. Manaus, AM, BrasilUniversidade de São Paulo. Instituto de Ciencias Biomedicas. Departamento de Parasitologia. São Paulo, SP, BrasilUniversidade de São Paulo. Instituto de Ciencias Biomedicas. Departamento de Parasitologia. São Paulo, SP, BrasilInstituto Nacional Para Pesquisa da Amazonia. Manaus, AM, BrasilUniversidade Federal do Rio Grande do Norte. Laboratorio de Malaria e Biologia da Toxoplasmose. Natal, RN, BrasilEmpresa Brasileira de Pesquisa Agricola Amazônia Ocidental. Manaus, AM, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Belo Horizonte, MG, Brasil/Universidade Federal de Minas Gerais. Escola de Farmacia. Belo Horizonte, MG, BrasilUniversidade Federal da Amazonas. Manaus, AM, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Belo Horizonte, MG, Brasil/Universidade Federal de Minas Gerais. Escola de Farmacia. Belo Horizonte, MG, BrasilInstituto Nacional Para Pesquisa da Amazonia. Manaus, AM, BrasilUniversidade Federal da Amazonas. Manaus, AM, Brasil4-Nerolidylcatechol (1) is an abundant antiplasmodial metabolite that is isolated from Piper peltatum roots.O-Acylation or O-alkylation of compound 1 provides derivatives exhibiting improved stability and significant in vitro antiplasmodial activity. The aim of this work was to study the in vitro inhibition of hemozoin formation, inhibition of isoprenoid biosynthesis in Plasmodium falciparum cultures, and in vivoantimalarial activity of several 4-nerolidylcatechol derivatives. 1,2-O,O-Diacetyl-4-nerolidylcatechol (2) inhibited in vitro hemozoin formation by up to 50%. In metabolic labeling studies using [1-(n)-3H]geranylgeranyl pyrophosphate, diester 2 significantly inhibited the biosynthesis of isoprenoid metabolites ubiquinone 8, menaquinone 4, and dolichol 12 in cultures of P. falciparum 3D7. Similarly, 2-O-benzyl-4-nerolidylcatechol (3) significantly inhibited the biosynthesis of dolichol 12. P. falciparum in vitroprotein synthesis was not affected by compounds 2 or 3. At oral doses of 50 mg per kg of body weight per day, compound 2 suppressed Plasmodium berghei NK65 in infected BALB/c mice by 44%. This in vivoresult for derivative 2 represents marked improvement over that obtained previously for natural product 1. Compound 2 was not detected in mouse blood 1 h after oral ingestion or in mixtures with mouse blood/blood plasma in vitro. However, it was detected after in vitro contact with human blood or blood plasma. Derivatives of 4-nerolidylcatechol exhibit parasite-specific modes of action, such as inhibition of isoprenoid biosynthesis and inhibition of hemozoin formation, and they therefore merit further investigation for their antimalarial potential.antiplasmodialPlasmodium bergheiantimalarialinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/12568/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALIn Vivo Antimalarial Activity and Mechanisms of Action of 4-.pdfIn Vivo Antimalarial Activity and Mechanisms of Action of 4-.pdfapplication/pdf4474170https://www.arca.fiocruz.br/bitstream/icict/12568/2/In%20Vivo%20Antimalarial%20Activity%20and%20Mechanisms%20of%20Action%20of%204-.pdf76a7fbc8de71cbc572c96806b9fe0380MD52TEXTIn Vivo Antimalarial Activity and Mechanisms of Action of 4-.pdf.txtIn Vivo Antimalarial Activity and Mechanisms of Action of 4-.pdf.txtExtracted texttext/plain10https://www.arca.fiocruz.br/bitstream/icict/12568/3/In%20Vivo%20Antimalarial%20Activity%20and%20Mechanisms%20of%20Action%20of%204-.pdf.txt2c6eb67c8897d916ae47524b1a844d3fMD53icict/125682019-06-19 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| dc.title.pt_BR.fl_str_mv |
In Vivo Antimalarial Activity and Mechanisms of Action of 4-Nerolidylcatechol Derivatives |
| title |
In Vivo Antimalarial Activity and Mechanisms of Action of 4-Nerolidylcatechol Derivatives |
| spellingShingle |
In Vivo Antimalarial Activity and Mechanisms of Action of 4-Nerolidylcatechol Derivatives Silva, Luiz Francisco Rocha e antiplasmodial Plasmodium berghei antimalarial |
| title_short |
In Vivo Antimalarial Activity and Mechanisms of Action of 4-Nerolidylcatechol Derivatives |
| title_full |
In Vivo Antimalarial Activity and Mechanisms of Action of 4-Nerolidylcatechol Derivatives |
| title_fullStr |
In Vivo Antimalarial Activity and Mechanisms of Action of 4-Nerolidylcatechol Derivatives |
| title_full_unstemmed |
In Vivo Antimalarial Activity and Mechanisms of Action of 4-Nerolidylcatechol Derivatives |
| title_sort |
In Vivo Antimalarial Activity and Mechanisms of Action of 4-Nerolidylcatechol Derivatives |
| author |
Silva, Luiz Francisco Rocha e |
| author_facet |
Silva, Luiz Francisco Rocha e Nogueira, Karla Lagos Pinto, Ana Cristina da Silva Katzin, Alejandro Miguel Sussmann, Rodrigo A. C. Muniz, Magno Perêa Neto, Valter Ferreira de Andrade Chaves, Francisco Célio Maia Coutinho, Julia Penna Lima, Emerson Silva Krettli, Antoniana Ursine Tadei, Wanderli Pedro Pohlit, Adrian Martin |
| author_role |
author |
| author2 |
Nogueira, Karla Lagos Pinto, Ana Cristina da Silva Katzin, Alejandro Miguel Sussmann, Rodrigo A. C. Muniz, Magno Perêa Neto, Valter Ferreira de Andrade Chaves, Francisco Célio Maia Coutinho, Julia Penna Lima, Emerson Silva Krettli, Antoniana Ursine Tadei, Wanderli Pedro Pohlit, Adrian Martin |
| author2_role |
author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Silva, Luiz Francisco Rocha e Nogueira, Karla Lagos Pinto, Ana Cristina da Silva Katzin, Alejandro Miguel Sussmann, Rodrigo A. C. Muniz, Magno Perêa Neto, Valter Ferreira de Andrade Chaves, Francisco Célio Maia Coutinho, Julia Penna Lima, Emerson Silva Krettli, Antoniana Ursine Tadei, Wanderli Pedro Pohlit, Adrian Martin |
| dc.subject.en.pt_BR.fl_str_mv |
antiplasmodial Plasmodium berghei antimalarial |
| topic |
antiplasmodial Plasmodium berghei antimalarial |
| description |
Instituto Nacional Para Pesquisa da Amazonia. Manaus, AM, Brasil/Universidade Federal da Amazonas. Manaus, AM, Brasil/Universidade Centro Norte. Manaus, AM, Brasil |
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2015 |
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2015 |
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2016-01-20T14:46:14Z |
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2016-01-20T14:46:14Z |
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SILVA, Luiz Francisco Rocha e et al. In Vivo Antimalarial Activity and Mechanisms of Action of 4-Nerolidylcatechol Derivatives. Antimicrob Agents Chemother., vol. 59, n. 6, p. 3271–3280, 2015. |
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https://www.arca.fiocruz.br/handle/icict/12568 |
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1098-6596 |
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10.1128/AAC.05012-14 |
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SILVA, Luiz Francisco Rocha e et al. In Vivo Antimalarial Activity and Mechanisms of Action of 4-Nerolidylcatechol Derivatives. Antimicrob Agents Chemother., vol. 59, n. 6, p. 3271–3280, 2015. 1098-6596 10.1128/AAC.05012-14 |
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American Society for Microbiology |
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