2. Academic Validation
  3. New insights into the mechanism of antifungal action of 8-hydroxyquinolines

New insights into the mechanism of antifungal action of 8-hydroxyquinolines

  • Saudi Pharm J. 2019 Jan;27(1):41-48. doi: 10.1016/j.jsps.2018.07.017.
Bruna Pippi 1,  William Lopes 2,  Paula Reginatto 1,  Fernanda Émili Klein Silva 3,  Angélica Rocha Joaquim 4,  Ricardo José Alves 5,  Gustavo Pozza Silveira 6,  Marilene Henning Vainstein 2,  Saulo Fernandes Andrade 1 4,  Alexandre Meneghello Fuentefria 1 4
Affiliations

Affiliations

  • 1 Programa de Pós-Graduação em Microbiologia Agrícola e do Ambiente, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
  • 2 Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
  • 3 Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
  • 4 Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
  • 5 Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
  • 6 Departamento de Química Orgânica, Instituto de Química, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
PMID: 30662305 DOI: 10.1016/j.jsps.2018.07.017
Abstract

The 8-hydroxyquinoline core is a privileged scaffold for drug design explored to afford novel derivatives endowed with biological activity. Our research aimed at clarifying the Antifungal mechanism of action of clioquinol, 8-hydroxy-5-quinolinesulfonic acid, and 8-hydroxy-7-iodo-5-quinolinesulfonic acid (three 8-hydroxyquinoline derivatives). The Antifungal mode of action of these derivatives on Candida spp. and dermatophytes was investigated using sorbitol protection assay, cellular leakage effect, ergosterol binding assay, and scanning electron microscopy. Clioquinol damaged the cell wall and inhibited the formation of pseudohyphae by C. albicans. The 8-hydroxy-5-quinolinesulfonic acid derivatives compromised the functional integrity of cytoplasmic membranes. To date no similar report was found about the Antifungal mechanism of 8-hydroxyquinolines. These results, combined with the broad Antifungal spectrum already demonstrated previously, reinforce the potential of 8-hydroxyquinolines for the development of new drugs.

Keywords

8-Hydroxyquinoline derivatives; Candida spp.; Clioquinol; Dermatophytes; Mechanism of action.

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