Effect of 3-Alkylpyridine Marine Alkaloid Analogues in Leishmania Species Related to American Cutaneous Leishmaniasis

Authors

  • Patrícia A. Machado,

    1. Departamento de Parasitologia, Microbiologia e Imunologia, Instituto de Ciências Biológicas; Universidade Federal de Juiz de Fora, Juiz de Fora, Minas Gerais, Brasil
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    • These authors contributed equally in this work.

  • Flaviane F. Hilário,

    1. Departamento de Química, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brasil
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    • These authors contributed equally in this work.

  • Lidiane O. Carvalho,

    1. Departamento de Parasitologia, Microbiologia e Imunologia, Instituto de Ciências Biológicas; Universidade Federal de Juiz de Fora, Juiz de Fora, Minas Gerais, Brasil
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  • Mariana L. T. Silveira,

    1. Departamento de Química, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brasil
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  • Rosemeire B. Alves,

    1. Departamento de Química, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brasil
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  • Rossimiriam P. Freitas,

    1. Departamento de Química, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brasil
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  • Elaine S. Coimbra

    Corresponding author
    1. Departamento de Parasitologia, Microbiologia e Imunologia, Instituto de Ciências Biológicas; Universidade Federal de Juiz de Fora, Juiz de Fora, Minas Gerais, Brasil
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Corresponding author: Elaine S. Coimbra,elaine.coimbra@ufjf.edu.br

Abstract

A series of oxygenated analogues of marine 3-alkylpyridine alkaloids were synthesized, and their leishmanicidal activity was assayed. All compounds were prepared from 3-pyridinepropanol in few steps and in good yields. The key step for the synthesis of these compounds was a classic Williamson etherification under phase-transfer conditions. Besides toxicity in peritoneal macrophages, the compounds exhibited a significant leishmanicidal activity. Of twelve compounds tested, five showed a strong leishmanicidal activity against promastigote forms of Leishmania amazonensis and L. braziliensis with IC50 below 10 μm. Compounds 11, 14, 15, and 16 showed a strong leishmanicidal activity on intracellular amastigotes (IC50 values of 2.78; 0.27; 1.03, and 1.33 μm, respectively), which is unlikely to be owing to the activation of nitric oxide production by macrophages.

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