Evaluation of naphthoquinones identified the acetylated isolapachol as a potent and selective antiplasmodium agent
| 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/17802 |
Resumo: | CNPq, FAPESB, FAPEAL e CAPES. |
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Moreira, Diogo Rodrigo MagalhãesSá, Matheus S. deMacedo, Taís SMenezes, Maria NReys, José Rui MSantana, Antônio E. GSilva, Thaissa LMaia, Gabriela L. ABarbosa Filho, José MariaCamara, Celso ASilva, Tania M. S. daSilva, Katia N. daGuimaraes, Elisalva TeixeiraSantos, Ricardo Ribeiro dosGoulart, Marília O. FSoares, Milena Botelho Pereira2017-02-13T16:20:17Z2017-02-13T16:20:17Z2015MOREIRA, D. R. M. et al. Evaluation of naphthoquinones identified the acetylated isolapachol as a potent and selective antiplasmodium agent. Journal of Enzyme Inhibition and Medicinal Chemistry, v. 30, n. 4, p. 615–621, 2014.1475-6366https://www.arca.fiocruz.br/handle/icict/1780210.3109/14756366.2014.958083CNPq, FAPESB, FAPEAL e CAPES.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.Universidade Federal de Alagoas. Instituto de Química e Biotecnologia. Maceió, AL, Brasil.Universidade Federal de Alagoas. Instituto de Química e Biotecnologia. Maceió, AL, Brasil.Universidade Federal de Alagoas. Instituto de Química e Biotecnologia. Maceió, AL, Brasil.Universidade Federal da Paraíba. Laboratório de Tecnologia Farmacêutica. João Pessoa, PB, Brasil.Universidade Federal da Paraíba. Laboratório de Tecnologia Farmacêutica. João Pessoa, PB, Brasil.Universidade Federal Rural de Pernambuco. Departamento de Química. Recife, PE, Brasil.Universidade Federal Rural de Pernambuco. Departamento de Química. Recife, PE, Brasil.Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil.Universidade Federal de Alagoas. Instituto de Química e Biotecnologia. Maceió, AL, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.This study reports on the design, synthesis and antiparasitic activity of three new semi-synthetic naphthoquinones structurally related to the naturally-occurring lapachol and lapachone. Of the compounds tested, 3-(3-methylbut-1-en-1-yl)-1,4-dioxo-1,4-dihydronaphthalen-2-yl acetate (1) was the most active against Plasmodium falciparum among both natural and semi-synthetic naphthoquinones, showing potent and selective activity. Compound 1 was able to reduce the in vitro parasite burden, in vitro parasite cell cycle, as well as the blood parasitemia in Plasmodium berghei-infected mice. More importantly, infection reduction under compound 1-treatment was achieved without exhibiting mouse genotoxicity. Regarding the molecular mechanism of action, this compound inhibited the hemozoin crystal formation in P. falciparum treated cells, and this was further confirmed by observing that it inhibits the β-hematin polymerization process similarly to chloroquine. Interestingly, this compound did not affect either mitochondria structure or cause DNA fragmentation in parasite treated cells. In conclusion, we identified a semi-synthetic antimalarial naphthoquinone closely related to isolapachol, which had stronger antimalarial activity than lapachol.engTaylor & FrancisAgentes antiparasitáriosHemozoinMaláriaMitocôndriaNaftoquinonasPlasmodium falciparumAntiparasitic agentsHemozoinMalariaMitochondriaNaphthoquinonesPlasmodium falciparumAntiparasitáriosMaláriaMitocôndriasNaftoquinonasPlasmodium falciparumEvaluation of naphthoquinones identified the acetylated isolapachol as a potent and selective antiplasmodium agentinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; 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| dc.title.pt_BR.fl_str_mv |
Evaluation of naphthoquinones identified the acetylated isolapachol as a potent and selective antiplasmodium agent |
| title |
Evaluation of naphthoquinones identified the acetylated isolapachol as a potent and selective antiplasmodium agent |
| spellingShingle |
Evaluation of naphthoquinones identified the acetylated isolapachol as a potent and selective antiplasmodium agent Moreira, Diogo Rodrigo Magalhães Agentes antiparasitários Hemozoin Malária Mitocôndria Naftoquinonas Plasmodium falciparum Antiparasitic agents Hemozoin Malaria Mitochondria Naphthoquinones Plasmodium falciparum Antiparasitários Malária Mitocôndrias Naftoquinonas Plasmodium falciparum |
| title_short |
Evaluation of naphthoquinones identified the acetylated isolapachol as a potent and selective antiplasmodium agent |
| title_full |
Evaluation of naphthoquinones identified the acetylated isolapachol as a potent and selective antiplasmodium agent |
| title_fullStr |
Evaluation of naphthoquinones identified the acetylated isolapachol as a potent and selective antiplasmodium agent |
| title_full_unstemmed |
Evaluation of naphthoquinones identified the acetylated isolapachol as a potent and selective antiplasmodium agent |
| title_sort |
Evaluation of naphthoquinones identified the acetylated isolapachol as a potent and selective antiplasmodium agent |
| author |
Moreira, Diogo Rodrigo Magalhães |
| author_facet |
Moreira, Diogo Rodrigo Magalhães Sá, Matheus S. de Macedo, Taís S Menezes, Maria N Reys, José Rui M Santana, Antônio E. G Silva, Thaissa L Maia, Gabriela L. A Barbosa Filho, José Maria Camara, Celso A Silva, Tania M. S. da Silva, Katia N. da Guimaraes, Elisalva Teixeira Santos, Ricardo Ribeiro dos Goulart, Marília O. F Soares, Milena Botelho Pereira |
| author_role |
author |
| author2 |
Sá, Matheus S. de Macedo, Taís S Menezes, Maria N Reys, José Rui M Santana, Antônio E. G Silva, Thaissa L Maia, Gabriela L. A Barbosa Filho, José Maria Camara, Celso A Silva, Tania M. S. da Silva, Katia N. da Guimaraes, Elisalva Teixeira Santos, Ricardo Ribeiro dos Goulart, Marília O. F Soares, Milena Botelho Pereira |
| author2_role |
author author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Moreira, Diogo Rodrigo Magalhães Sá, Matheus S. de Macedo, Taís S Menezes, Maria N Reys, José Rui M Santana, Antônio E. G Silva, Thaissa L Maia, Gabriela L. A Barbosa Filho, José Maria Camara, Celso A Silva, Tania M. S. da Silva, Katia N. da Guimaraes, Elisalva Teixeira Santos, Ricardo Ribeiro dos Goulart, Marília O. F Soares, Milena Botelho Pereira |
| dc.subject.other.pt_BR.fl_str_mv |
Agentes antiparasitários Hemozoin Malária Mitocôndria Naftoquinonas Plasmodium falciparum |
| topic |
Agentes antiparasitários Hemozoin Malária Mitocôndria Naftoquinonas Plasmodium falciparum Antiparasitic agents Hemozoin Malaria Mitochondria Naphthoquinones Plasmodium falciparum Antiparasitários Malária Mitocôndrias Naftoquinonas Plasmodium falciparum |
| dc.subject.en.pt_BR.fl_str_mv |
Antiparasitic agents Hemozoin Malaria Mitochondria Naphthoquinones Plasmodium falciparum |
| dc.subject.decs.pt_BR.fl_str_mv |
Antiparasitários Malária Mitocôndrias Naftoquinonas Plasmodium falciparum |
| description |
CNPq, FAPESB, FAPEAL e CAPES. |
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2015 |
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2015 |
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2017-02-13T16:20:17Z |
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2017-02-13T16:20:17Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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MOREIRA, D. R. M. et al. Evaluation of naphthoquinones identified the acetylated isolapachol as a potent and selective antiplasmodium agent. Journal of Enzyme Inhibition and Medicinal Chemistry, v. 30, n. 4, p. 615–621, 2014. |
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https://www.arca.fiocruz.br/handle/icict/17802 |
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1475-6366 |
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10.3109/14756366.2014.958083 |
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MOREIRA, D. R. M. et al. Evaluation of naphthoquinones identified the acetylated isolapachol as a potent and selective antiplasmodium agent. Journal of Enzyme Inhibition and Medicinal Chemistry, v. 30, n. 4, p. 615–621, 2014. 1475-6366 10.3109/14756366.2014.958083 |
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Taylor & Francis |
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Taylor & Francis |
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