Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/19662
Title: 1,10-Phenanthroline-5,6-Dione-Based Compounds Are Effective in Disturbing Crucial Physiological Events of Phialophora verrucosa
Authors: Granato, Marcela Queiroz
Gonçalves, Diego de Souza
Seabra, Sergio Henrique
McCann, Malachy
Devereux, Michael
Santos, André Luis Souza dos
Kneipp, Lucimar Ferreira
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Taxonomia, Bioquímica e Bioprospecção de Fungos. Rio de Janeiro, RJ. Brasil.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Microbiologia Geral. Laboratório de Investigação de Peptidases. Rio de Janeiro, RJ, Brasil / Universidade Federal do Ri de Janeiro. Instituto de Química. Programa de Pós-Graduação em Bioquímica. Rio de Janeiro, RJ, Brasil.
Centro Universitário Estadual da Zona Oeste. Laboratório de Tecnologia em Cultura de Células. Duque de Caxias, RJ, Brasil.
National University of Ireland. Maynooth Universit. Chemistry Department. Maynooth, Ireland.
Dublin Institute of Technolog. , Focas Research Institute. Centre for Biomimetic and Therapeutic Research. Dublin, Ireland.
Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Microbiologia Geral. Laboratório de Investigação de Peptidases. Rio de Janeiro, RJ, Brasil / Universidade Federal do Ri de Janeiro. Instituto de Química. Programa de Pós-Graduação em Bioquímica. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Taxonomia, Bioquímica e Bioprospecção de Fungos. Rio de Janeiro, RJ. Brasil.
Abstract: Phialophora verrucosa is a dematiaceous fungus able to cause chromoblastomycosis, phaeohyphomycosis and mycetoma. All these fungal diseases are extremely difficult to treat and often refractory to the current therapeutic approaches. Therefore, there is an urgent necessity to develop new antifungal agents to combat these mycoses. In this context, the aim of the present work was to investigate the effect of 1,10-phenanthroline-5,6-dione (phendione) and its metal-based derivatives [Ag(phendione)2]ClO4 = ([Ag(phendione)2](+)) and [Cu(phendione)3](ClO4)2.4H2O = ([Cu(phendione)3](2+)) on crucial physiological events of P. verrucosa conidial cells. Using the CLSI protocol, we have shown that phendione, [Ag(phendione)2](+) and [Cu(phendione)3](2+) were able to inhibit fungal proliferation, presenting MIC/IC50 values of 12.0/7.0, 4.0/2.4, and 5.0/1.8 μM, respectively. [Cu(phendione)3](2+) had fungicidal action and when combined with amphotericin B, both at sub-MIC (½ × MIC) concentrations, significantly reduced (~40%) the fungal growth. Cell morphology changes inflicted by phendione and its metal-based derivatives was corroborated by scanning electron microscopy, which revealed irreversible ultrastructural changes like surface invaginations, cell disruption and shrinkages. Furthermore, [Cu(phendione)3](2+) and [Ag(phendione)2](+) were able to inhibit metallopeptidase activity secreted by P. verrucosa conidia by approximately 85 and 40%, respectively. Ergosterol content was reduced (~50%) after the treatment of P. verrucosa conidial cells with both phendione and [Ag(phendione)2](+). To different degrees, all of the test compounds were able to disturb the P. verrucosa conidia-into-mycelia transformation. Phendione and its Ag(+) and Cu(2+) complexes may represent a promising new group of antimicrobial agents effective at inhibiting P. verrucosa growth and morphogenesis.
Keywords: Phialophora verrucosa
1,10-phenanthroline-5,6-dione
metal-based drugs
antifungal activity
chromoblastomycosis
keywords: Cromoblastomicose
Atividade antifúngica
Drogas à base de metal
Phialophora verrucosa
1,10-fenantrolina-5,6-diona
Issue Date: 2017
Publisher: Frontiers Media
Citation: GRANATO, Marcela Queiroz; et al. 1,10-Phenanthroline-5,6-Dione-Based Compounds Are Effective in Disturbing Crucial Physiological Events of Phialophora verrucosa. Front Microbiol., v.8, Article 76, 9p, Jan. 2017.
DOI: 10.3389/fmicb.2017.00076
ISSN: 1664-302X
Copyright: open access
Appears in Collections:IOC - Artigos de Periódicos

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