Synthesis of Isosteric Triterpenoid Derivatives and Antifungal Activity

Authors

  • Adrine Innocente,

    1. Laboratório de Fitoquímica e Síntese Orgânica, Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
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  • Bruna B. Casanova,

    1. Laboratório de Fitoquímica e Síntese Orgânica, Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
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  • Fernanda Klein,

    1. Laboratório de Micologia Aplicada, Departamento de Análises, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
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  • Aline D. Lana,

    1. Laboratório de Micologia Aplicada, Departamento de Análises, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
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  • Dariane Pereira,

    1. Laboratório de Micologia Aplicada, Departamento de Análises, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
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  • Mauro N. Muniz,

    1. Laboratório de Fitoquímica e Síntese Orgânica, Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
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  • Pascal Sonnet,

    1. Laboratoire des Glucides, FRE CNRS 3517, UFR de Pharmacie Université de Picardie Jules Verne1, Rue des Louvels, Amiens Cedex 1, France
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  • Grace Gosmann,

    1. Laboratório de Fitoquímica e Síntese Orgânica, Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
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  • Alexandre M. Fuentefria,

    1. Laboratório de Micologia Aplicada, Departamento de Análises, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
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  • Simone C. B. Gnoatto

    Corresponding author
    1. Laboratório de Fitoquímica e Síntese Orgânica, Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
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Abstract

Dermatomycoses are among the most widespread and common superficial and cutaneous fungal infections in humans. There is an urgent need to develop efficient and non-toxic antimycotic agents with a specific spectrum of activity. Triterpenes have been demonstrated to exhibit a wide range of biological activities, including antifungal activities. In this study, through hemisynthesis, we aimed to obtain triterpene-isosteric molecules from betulinic and ursolic acids to improve the antifungal activity and spectrum of action of these compounds. Six compounds were resynthesized and tested against eleven mucocutaneous and cutaneous mycotic agents. The results of the susceptibility assays were expressed as the minimal inhibitory concentration (MIC). The MIC values of the piperazinyl derivatives of ursolic and betulinic acids that were active against pathogenic yeasts were in the range of 16–32 μg/mL and 4–16 μg/mL, respectively, whereas fungicidal effects were observed at concentrations ranging from 16 to 128 μg/mL and 8 to 128 μg/mL, respectively. The piperazinyl derivative of betulinic acid exhibited an antifungal profile similar to that of terbinafine and was the most effective derivative against dermatophytes. This strategy led to a promising candidate for the development of a new antifungal agent.

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