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2-(Benzylideneamino)phenol: A Promising Hydroxyaldimine with Potent Activity Against Dermatophytoses

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Abstract

Infections caused by dermatophytes, mainly Trichophyton rubrum,are often vulnerable to relapses upon cessation of antifungal therapy, reinforcing the need of new antifungals. Aldimines have potential biological activities, but there are few reports on their antifungal profile. The aim of this study was to evaluate the antifungal activity of 2-(benzylideneamino)phenol (3A3) and 4-(benzylideneamino)phenol (3A4) against dermatophytes. We determined the minimum inhibitory concentration, minimum fungicidal concentration, time-kill curves and fractional inhibitory concentration of the combination of 3A3, 3A4 and itraconazole against a set of isolates of T. rubrum and T. interdigitale. 3A3 was tested in a murine model of dermatophytoses caused by T. rubrum, and the effect on phagocytosis was assessed. The MIC values ranged from 8 to 32 μg/mL for 3A3 and from 64 to 256 μg/mL for 3A4. The interaction between 3A3 and 3A4 with itraconazole proved to be synergistic and indifferent, respectively. 3A3 was as efficient as itraconazole in reducing the fungal burden on the skin of mice, being this effect associated with the influx of neutrophil and macrophage. Also, 3A3 was able to increase the internalization of conidia by macrophages. Altogether, our data encourage future clinical studies with 3A3 to treat dermatophytoses.

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Acknowledgments

The authors thank to Pharlab (Brazil) for the donation of itraconazole standard powder. This work was supported by Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG Grant CBB-APQ-00874-11); Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); Universidade Federal de Minas Gerais (Programa de Auxílio à Pesquisa de Doutores Recém-Contratados); and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq Grant 471894/2011-7).

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The authors reported no conflict of interest.

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Authors and Affiliations

  1. Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av Antônio Carlos 6627, Belo Horizonte, Minas Gerais, CEP 31260-901, Brazil

    Alan Kiill Gasparto, Ludmila Matos Baltazar, Ludmila Ferreira Gouveia, Maria Aparecida de Resende-Stoianoff & Daniel Assis Santos

  2. Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Cleiton Moreira da Silva & Angelo de Fátima

  3. Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Ricardo Martins Duarte Byrro & Armando da Silva Cunha Júnior

  4. Laboratório de Apoptose, Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Milene Alvarenga Rachid

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  1. Alan Kiill Gasparto
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  2. Ludmila Matos Baltazar
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Correspondence to Daniel Assis Santos.

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Gasparto, A.K., Baltazar, L.M., Gouveia, L.F. et al. 2-(Benzylideneamino)phenol: A Promising Hydroxyaldimine with Potent Activity Against Dermatophytoses. Mycopathologia 179, 243–251 (2015). https://doi.org/10.1007/s11046-014-9850-5

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