International Journal of Travel Medicine and Global Health

International Journal of Travel Medicine and Global Health

Halogenation as a Strategy to Improve Antiplasmodial Activity: A Report of New 3-Alkylpyridine Marine Alkaloid Analogs

Document Type : Original Article

Authors
Camila de Souza Barbosa 1
Daniel Silqueira Martins Guimarães 2
Juliana da Costa Alves 1
Cristiana Ferreira Alves de Brito 3
Renato Márcio Ribeiro-Viana 4
Fernando de Pilla Varotti 1
Gustavo Henrique Ribeiro Viana 1
1 Núcleo de Pesquisa em Química Biológica, Universidade Federal de São João Del-Rei, Campus Centro Oeste, Divinópolis, MG 35501-296, Brazil
2 Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, MG 30190-009, Brazil
3 Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, MG 30190-009, Brazil
4 Departamento Acadêmico de Química (DAQUI), Universidade Tecnológica Federal do Paraná, 86036-370 Londrina, Paraná, Brazil
10.15171/ijtmgh.2019.27
Abstract
Introduction: 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 Plasmodium falciparum.
Methods: 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.
Results: Compounds 6 and 7 showed improved antiplasmodial activities (IC50 = 7.2 and 8.3 μM, respectively) 20 times higher than that of their precursor, compound 5 (IC50 = 210.7 μM). Ultraviolet-visible titration experiments demonstrated that halogenation of compound 5 did not alter its ability to bind its target, hematin.
Conclusion: Halogenation can enhance the antiplasmodial activity of a compound without altering its mechanism of action.
Keywords
Plasmodium falciparum
3-Alkylpyridine Marine Alkaloid Analogs
Antiplasmodial Activity
Halogenation
Malaria
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International Journal of Travel Medicine and Global Health
Volume 7, Issue 4 - Serial Number 27
Autumn 2019
Pages 129-134

  • Receive Date 18 August 2019
  • Revise Date 26 October 2019
  • Accept Date 29 November 2019