Halogenation as a Strategy to Improve Antiplasmodial Activity: A Report of New 3-Alkylpyridine Marine Alkaloid Analogs
<strong>Introduction:</strong> Due to the emergence of resistance to antimalarial drugs as well as the lack of vaccination for malaria, there is an urgent demand for the development of new antimalarial alternatives. Recently, our research group developed a new set of 3-alkylpyridine mari...
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doaj-5c739a1137464ddda626467c4495f4032020-11-25T02:14:59ZengInternational Travel Medicine Center of IranInternational Journal of Travel Medicine and Global Health2322-11002476-57592019-12-017412913410.15171/ijtmgh.2019.2799026Halogenation as a Strategy to Improve Antiplasmodial Activity: A Report of New 3-Alkylpyridine Marine Alkaloid AnalogsCamila Barbosa0Daniel Guimarães1Juliana Alves2Cristiana de Brito3Renato Ribeiro-Viana4Fernando Varotti5Gustavo Viana6Núcleo de Pesquisa em Química Biológica, Universidade Federal de São João Del-Rei, Campus Centro Oeste, Divinópolis, MG 35501-296, BrazilInstituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, MG 30190-009, BrazilNúcleo de Pesquisa em Química Biológica, Universidade Federal de São João Del-Rei, Campus Centro Oeste, Divinópolis, MG 35501-296, BrazilInstituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, MG 30190-009, BrazilDepartamento Acadêmico de Química (DAQUI), Universidade Tecnológica Federal do Paraná, 86036-370 Londrina, Paraná, BrazilNúcleo de Pesquisa em Química Biológica, Universidade Federal de São João Del-Rei, Campus Centro Oeste, Divinópolis, MG 35501-296, BrazilNúcleo de Pesquisa em Química Biológica, Universidade Federal de São João Del-Rei, Campus Centro Oeste, Divinópolis, MG 35501-296, Brazil<strong>Introduction:</strong> Due to the emergence of resistance to antimalarial drugs as well as the lack of vaccination for malaria, there is an urgent demand for the development of new antimalarial alternatives. Recently, our research group developed a new set of 3-alkylpyridine marine alkaloid analogs, of which a compound known as compound 5 was found to be inactive against <em>Plasmodium falciparum</em>.<br /> <strong>Methods:</strong> Herein, we report a successful halogenation strategy to improve the antiplasmodial activity of compound 5 through the replacement of a hydroxyl group by chlorine (compound 6) and fluorine (compound 7) atoms.<br /> <strong>Results:</strong> Compounds 6 and 7 showed improved antiplasmodial activities (IC<sub>50</sub> = 7.2 and 8.3 μM, respectively) 20 times higher than that of their precursor, compound 5 (IC<sub>50</sub> = 210.7 μM). Ultraviolet-visible titration experiments demonstrated that halogenation of compound 5 did not alter its ability to bind its target, hematin.<br /> <strong>Conclusion:</strong> Halogenation can enhance the antiplasmodial activity of a compound without altering its mechanism of action.http://www.ijtmgh.com/article_99026_597db8b98dcb4ac2efac72b6a2a999b3.pdfplasmodium falciparum3-alkylpyridine marine alkaloid analogsantiplasmodial activityhalogenationmalaria |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Camila Barbosa Daniel Guimarães Juliana Alves Cristiana de Brito Renato Ribeiro-Viana Fernando Varotti Gustavo Viana |
spellingShingle |
Camila Barbosa Daniel Guimarães Juliana Alves Cristiana de Brito Renato Ribeiro-Viana Fernando Varotti Gustavo Viana Halogenation as a Strategy to Improve Antiplasmodial Activity: A Report of New 3-Alkylpyridine Marine Alkaloid Analogs International Journal of Travel Medicine and Global Health plasmodium falciparum 3-alkylpyridine marine alkaloid analogs antiplasmodial activity halogenation malaria |
author_facet |
Camila Barbosa Daniel Guimarães Juliana Alves Cristiana de Brito Renato Ribeiro-Viana Fernando Varotti Gustavo Viana |
author_sort |
Camila Barbosa |
title |
Halogenation as a Strategy to Improve Antiplasmodial Activity: A Report of New 3-Alkylpyridine Marine Alkaloid Analogs |
title_short |
Halogenation as a Strategy to Improve Antiplasmodial Activity: A Report of New 3-Alkylpyridine Marine Alkaloid Analogs |
title_full |
Halogenation as a Strategy to Improve Antiplasmodial Activity: A Report of New 3-Alkylpyridine Marine Alkaloid Analogs |
title_fullStr |
Halogenation as a Strategy to Improve Antiplasmodial Activity: A Report of New 3-Alkylpyridine Marine Alkaloid Analogs |
title_full_unstemmed |
Halogenation as a Strategy to Improve Antiplasmodial Activity: A Report of New 3-Alkylpyridine Marine Alkaloid Analogs |
title_sort |
halogenation as a strategy to improve antiplasmodial activity: a report of new 3-alkylpyridine marine alkaloid analogs |
publisher |
International Travel Medicine Center of Iran |
series |
International Journal of Travel Medicine and Global Health |
issn |
2322-1100 2476-5759 |
publishDate |
2019-12-01 |
description |
<strong>Introduction:</strong> Due to the emergence of resistance to antimalarial drugs as well as the lack of vaccination for malaria, there is an urgent demand for the development of new antimalarial alternatives. Recently, our research group developed a new set of 3-alkylpyridine marine alkaloid analogs, of which a compound known as compound 5 was found to be inactive against <em>Plasmodium falciparum</em>.<br /> <strong>Methods:</strong> Herein, we report a successful halogenation strategy to improve the antiplasmodial activity of compound 5 through the replacement of a hydroxyl group by chlorine (compound 6) and fluorine (compound 7) atoms.<br /> <strong>Results:</strong> Compounds 6 and 7 showed improved antiplasmodial activities (IC<sub>50</sub> = 7.2 and 8.3 μM, respectively) 20 times higher than that of their precursor, compound 5 (IC<sub>50</sub> = 210.7 μM). Ultraviolet-visible titration experiments demonstrated that halogenation of compound 5 did not alter its ability to bind its target, hematin.<br /> <strong>Conclusion:</strong> Halogenation can enhance the antiplasmodial activity of a compound without altering its mechanism of action. |
topic |
plasmodium falciparum 3-alkylpyridine marine alkaloid analogs antiplasmodial activity halogenation malaria |
url |
http://www.ijtmgh.com/article_99026_597db8b98dcb4ac2efac72b6a2a999b3.pdf |
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