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Exploring 1,2,3-triazole derivatives by using in vitro and in silico assays to target new antifungal agents and treat Candidiasis

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Abstract

Candidiasis is a serious public health problem that currently affects not only immunodeficient patients with predisposing conditions, but also immunocompetent individuals. Thus, the search for new antifungal agents is required also due to the emergence of resistant strains and to the side effects of the available drugs. The aim of this study is to evaluate the in vitro antifungal profile of nine synthetic 1,2,3-triazole derivatives against four Candida species of medical importance (C. albicans, C. tropicalis, C. parapsilosis, and C. krusei), as well as to identify their in silico structure-activity relationship. Interestingly, the antifungal susceptibility tests showed the compound 5-methyl-1-(phenylamino)-1H-1,2,3-triazol-4-yl-methanol (2b) with the lowest minimal inhibitory concentration value against C. albicans strain (MIC = 8 μg/mL) similar to other promissing compounds described in the literature. According to our in silico evaluation, some stereoelectronic properties (e.g., higher values of log S and lowest unoccupied molecular orbital energy and lower number of atoms, rotatable bonds and Hydrogen bond acceptors) were correlated with the antifungal activity detected. This series reinforced the potential of 1,2,3-triazole as a promising nucleus in the search for new antifungals and may help on designing new drugs for candidiasis.

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Acknowledgements

This work was supported by Research Support Foundation of the State of Rio de Janeiro (FAPERJ) and Postgraduate Scholarship from Educational Foundation of Macaé (FUNEMAC).

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Authors and Affiliations

  1. LAMCIFAR, Laboratório de Modelagem molecular e Pesquisa em Ciências Farmacêuticas, Universidade Federal do Rio de Janeiro, Campus Macaé, Av. São José do Barreto, 764, São José do Barreto, Macaé, RJ, CEP 27965-045, Brazil

    Taísa F. Santos, Jéssica B. de Jesus & Paula A. Abreu

  2. ModMolQSAR, Faculdade de Farmácia, UFRJ, Universidade Federal do Rio de Janeiro, Ilha do Fundão, Rio de Janeiro, RJ, CEP 21941599, Brazil

    Jéssica B. de Jesus & Carlos R. Rodrigues

  3. Laboratório de Micologia, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Ilha do Fundão, Rio de Janeiro, RJ, CEP 21941590, Brazil

    Paulo M. Neufeld

  4. Departamento de Química Orgânica, Programa de Pós-Graduação em Química, Universidade Federal Fluminense, Niterói, RJ, 24020-141, Brazil

    Alessandro K. Jordão, Vinícius R. Campos, Anna C. Cunha, Maria C. B. V. de Souza & Vitor F. Ferreira

  5. Unidade Universitária de Farmácia, Fundação Centro Universitário Estadual da Zona Oeste, UEZO, Rio de Janeiro, Rio de Janeiro, RJ, CEP 23070200, Brazil

    Alessandro K. Jordão

  6. PPBI, Instituto de Biologia, Campus Valonguinho, Niterói, RJ, CEP 24210130, Brazil

    Helena C. Castro

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  1. Taísa F. Santos
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  2. Jéssica B. de Jesus
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  3. Paulo M. Neufeld
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  4. Alessandro K. Jordão
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  7. Helena C. Castro
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  8. Maria C. B. V. de Souza
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  9. Vitor F. Ferreira
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  11. Paula A. Abreu
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Correspondence to Paula A. Abreu.

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Santos, T.F., de Jesus, J.B., Neufeld, P.M. et al. Exploring 1,2,3-triazole derivatives by using in vitro and in silico assays to target new antifungal agents and treat Candidiasis. Med Chem Res 26, 680–689 (2017). https://doi.org/10.1007/s00044-017-1789-x

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