• Title of article

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

  • Author/Authors

    Barbosa, Camila de Souza Núcleo de Pesquisa em Química Biológica - Universidade Federal de São João Del-Rei, Campus Centro Oeste, Divinópolis, Brazil , Guimarães, Daniel Silqueira Martins Instituto René Rachou - Fundação Oswaldo Cruz - Belo Horizonte, Brazil , Alves, Juliana da Costa Núcleo de Pesquisa em Química Biológica - Universidade Federal de São João Del-Rei, Campus Centro Oeste, Divinópolis, Brazil , Brito, Cristiana Ferreira Alves de Instituto René Rachou - Fundação Oswaldo Cruz - Belo Horizonte, Brazil , Ribeiro-Viana, Renato Márcio Departamento Acadêmico de Química (DAQUI) - Universidade Tecnológica Federal do Paraná, Paraná, Brazil , Varotti, Fernando de Pilla Núcleo de Pesquisa em Química Biológica - Universidade Federal de São João Del-Rei, Campus Centro Oeste, Divinópolis, Brazil , Viana, Gustavo Henrique Ribeiro Núcleo de Pesquisa em Química Biológica - Universidade Federal de São João Del-Rei, Campus Centro Oeste, Divinópolis, Brazil

  • Pages
    6
  • From page
    129
  • To page
    134
  • 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
    Malaria , Halogenation , Antiplasmodial Activity , 3-Alkylpyridine Marine Alkaloid Analogs , Plasmodium falciparum
  • Serial Year
    2019
  • Record number

    2497386

    • Link To Document
    https://search.isc.ac/dl/search/defaultta.aspx?DTC=10&DC=2497386