Silver(I) and Copper(II) Complexes of 1,10-Phenanthroline-5,6-Dione Against Phialophora verrucosa : A Focus on the Interaction With Human Macrophages and Galleria mellonella Larvae.

Autor:	Granato MQ; Laboratório de Taxonomia, Bioquímica e Bioprospecção de Fungos (LTBBF), Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil., Mello TP; Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes (LEAMER), Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil., Nascimento RS; Laboratório de Citotoxicidade e Genotoxicidade (LaCiGen), Instituto de Química, UFRJ, Rio de Janeiro, Brazil., Pereira MD; Laboratório de Citotoxicidade e Genotoxicidade (LaCiGen), Instituto de Química, UFRJ, Rio de Janeiro, Brazil., Rosa TLSA; Laboratório de Microbiologia Celular, IOC/FIOCRUZ, Rio de Janeiro, Brazil., Pessolani MCV; Laboratório de Microbiologia Celular, IOC/FIOCRUZ, Rio de Janeiro, Brazil., McCann M; Department of Chemistry, Maynooth University, National University of Ireland, Maynooth, Ireland., Devereux M; Center for Biomimetic and Therapeutic Research, Focas Research Institute, Technological University Dublin, Dublin, Ireland., Branquinha MH; Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes (LEAMER), Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil., Santos ALS; Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes (LEAMER), Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.; Laboratório de Citotoxicidade e Genotoxicidade (LaCiGen), Instituto de Química, UFRJ, Rio de Janeiro, Brazil., Kneipp LF; Laboratório de Taxonomia, Bioquímica e Bioprospecção de Fungos (LTBBF), Instituto Oswaldo Cruz (IOC), Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil.
Jazyk:	angličtina
Zdroj:	Frontiers in microbiology [Front Microbiol] 2021 Apr 27; Vol. 12, pp. 641258. Date of Electronic Publication: 2021 Apr 27 (Print Publication: 2021).
DOI:	10.3389/fmicb.2021.641258
Abstrakt:	Phialophora verrucosa is a dematiaceous fungus that causes mainly chromoblastomycosis, but also disseminated infections such as phaeohyphomycosis and mycetoma. These diseases are extremely hard to treat and often refractory to current antifungal therapies. In this work, we have evaluated the effect of 1,10-phenanthroline-5,6-dione (phendione) and its metal-based complexes, [Ag (phendione) 2 ]ClO 4 and [Cu(phendione) 3 ](ClO 4 ) 2 .4H 2 O, against P. verrucosa , focusing on (i) conidial viability when combined with amphotericin B (AmB); (ii) biofilm formation and disarticulation events; (iii) in vitro interaction with human macrophages; and (iv) in vivo infection of Galleria mellonella larvae. The combination of AmB with each of the test compounds promoted the additive inhibition of P. verrucosa growth, as judged by the checkerboard assay. During the biofilm formation process over polystyrene surface, sub-minimum inhibitory concentrations (MIC) of phendione and its silver(I) and copper(II) complexes were able to reduce biomass and extracellular matrix production. Moreover, a mature biofilm treated with high concentrations of the test compounds diminished biofilm viability in a concentration-dependent manner. Pre-treatment of conidial cells with the test compounds did not alter the percentage of infected THP-1 macrophages; however, [Ag(phendione) 2 ]ClO 4 caused a significant reduction in the number of intracellular fungal cells compared to the untreated system. In addition, the killing process was significantly enhanced by post-treatment of infected macrophages with the test compounds. P. verrucosa induced a typically cell density-dependent effect on G. mellonella larvae death after 7 days of infection. Interestingly, exposure to the silver(I) complex protected the larvae from P. verrucosa infection. Collectively, the results corroborate the promising therapeutic potential of phendione-based drugs against fungal infections, including those caused by P. verrucosa . Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Granato, Mello, Nascimento, Pereira, Rosa, Pessolani, McCann, Devereux, Branquinha, Santos and Kneipp.)
Databáze:	MEDLINE
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