The Antibacterial Synthetic Flavonoid BrCl-Flav Exhibits Important Anti-<i>Candida</i> Activity by Damaging Cell Membrane Integrity

Infections caused by <i>Candida</i> are very difficult to treat due to increasing antifungal resistance. Recent studies showed that patients with <i>Candida</i> infections resistant to fluconazole have very few treatment options. Therefore, finding new efficient antifungal ag...

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Autores principales: Cornelia Babii, Mihaela Savu, Iuliana Motrescu, Lucian Mihail Birsa, Laura Gabriela Sarbu, Marius Stefan
Formato: article
Lenguaje:EN
Publicado: MDPI AG 2021
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R
Acceso en línea:https://doaj.org/article/8a8925e98d8d423eaba9dfc7543925c5
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Sumario:Infections caused by <i>Candida</i> are very difficult to treat due to increasing antifungal resistance. Recent studies showed that patients with <i>Candida</i> infections resistant to fluconazole have very few treatment options. Therefore, finding new efficient antifungal agents is a matter of medical high priority. The aim of this study was to explore the antifungal potential of BrCl-flav-a representative of a new class of synthetic flavonoids with bromine as halogen substituent at the benzopyran core against four <i>Candida</i> clinical strains. Determination of minimum inhibitory concentration and minimum fungicidal concentration along with the time kill assay indicated a strong antifungal effect of BrCl-flav against <i>C. albicans</i>, <i>C. parapsilosis</i>, <i>C. krusei</i> and <i>C. glabrata</i>. The investigation of anti-<i>Candida</i> mechanism of action using fluorescence microscopy and scanning electron microscopy revealed that Br-Cl flav could inhibit fungal growth by impairing the membrane integrity, the resulting structural damages leading to cell lysis. BrCl-flav also showed important anti-virulence properties against <i>Candida</i> spp., inhibiting biofilm formation and yeast to hyphal transition. A strong synergistic antifungal effect against <i>C. albicans</i> strain was observed when BrCl-flav was used in combination with fluconazole. BrCl-flav has a good potential to develop new effective antifungal agents in the context of <i>Candida</i> spp. multidrug resistance phenomenon.