| Congresso Brasileiro de Microbiologia 2023 | Resumo: 245-1 | ||||
Resumo:Histoplasmosis is an endemic fungal infection in Brazil caused by Histoplasma capsulatum, a dimorphic fungus. Both immunocompromised and immunocompetent individuals can become infected by inhaling the fungal spores present in the soil of endemic regions, but HIV-positive patients are at a greater risk for the disseminated form of the disease. The current treatment for histoplasmosis involves the use of Itraconazol and Amphotericin B, which are costly and have high toxicity. Metal chelating agents such as 1,10-phenanthroline and its derivatives, including Phendione, [Ag(phendione)2] +, and [Cu(phendione)3] 2+, represent potential alternatives for antimicrobial treatment due to their ability to inhibit several biological processes of various pathogens, as well as their synthetic simplicity and low production cost. The aim of this study was to investigate the potential antifungal effects of 1,10-phenanthroline-5,6-dione (phendione) and its metallic derivatives on H. capsulatum yeasts. The susceptibility test of yeasts to these compounds was performed using the broth microdilution method, following the M27-A3 protocol with some modifications. The minimum inhibitory concentration (MIC) values for all 1,10-phenanthroline derivatives were lower than 0.5mg/L. However, when comparing the molar concentrations of the same compounds, the copper-complexed phendione showed greater antifungal activity (Phendione and [Ag(phendione)2]+: 0.78mM, [Cu(phendione)3]2+: 0.39mM). The synergistic/additive effect of the compounds, in association with Amphotericin B and Itraconazole, was analyzed using the checkerboard method, and in all of the different associations, an additive effect was observed. H. capsulatum yeasts can form biofilms, and the presence of phendione and its metallic derivatives altered the viability of these cells after treatment at doses higher than those observed for the MIC of all compounds. Although scanning electron microscopy and energy dispersion spectroscopy revealed that there was no morphological change of H. capsulatum yeasts when incubated with IC50 of phendione and its derivatives associated with silver and copper, during the process of transmission electron microscopy, our analysis has revealed modifications in the internal morphology of the observed yeast cells, concomitant with the presence of a tenuous membranous structure, indicating cellular damage. These observed changes could be a contributory factor to the eventual cellular death of the yeast. Preliminary data suggests that compounds derived from 1,10-phenanthroline, especially those associated with silver and copper metals, may represent potential alternatives for the treatment of histoplasmosis. Palavras-chave: Histoplasma capsulatum, Metal-based drugs, Antifungal activity Agência de fomento:CAPES, CNPQ e FAPERJ | |||||