Wydział Medyczny / Faculty of Medicine

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https://hdl.handle.net/20.500.12153/25
* Instytut Nauk Biologicznych * Instytut Nauk o Zdrowiu * Instytut Nauk Medycznych * Centrum Badań Eksperymentalnych

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Browsing Wydział Medyczny / Faculty of Medicine by Subject "4-AN"

Now showing 1 - 2 of 2
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    Antifungal Agent 4-AN Changes the Genome-Wide Expression Profile, Downregulates Virulence-Associated Genes and Induces Necrosis in Candida albicans Cells
    (MDPI, 2020) Martyna, Aleksandra; Masłyk, Maciej; Janeczko, Monika; Kochanowicz, Elżbieta; Gielniewski, Bartłomiej; Świercz, Aleksandra; Demchuk, Oleg M.; Kubiński, Konrad
    In the light of the increasing occurrence of antifungal resistance, there is an urgent need to search for new therapeutic strategies to overcome this phenomenon. One of the applied approaches is the synthesis of small-molecule compounds showing antifungal properties. Here we present a continuation of the research on the recently discovered anti-Candida albicans agent 4-AN. Using next generation sequencing and transcriptional analysis, we revealed that the treatment of C. albicans with 4-AN can change the expression profile of a large number of genes. The highest upregulation was observed in the case of genes involved in cell stress, while the highest downregulation was shown for genes coding sugar transporters. Real-time PCR analysis revealed 4-AN mediated reduction of the relative expression of genes engaged in fungal virulence (ALS1, ALS3, BCR1, CPH1, ECE1, EFG1, HWP1, HYR1 and SAP1). The determination of the fractional inhibitory concentration index (FICI) showed that the combination of 4-AN with amphotericin B is synergistic. Finally, flow cytometry analysis revealed that the compound induces mainly necrosis in C. albicans cells.
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    The Anti-Candida albicans Agent 4-AN Inhibits Multiple Protein Kinases
    (MDPI, 2019) Masłyk, Maciej; Janeczko, Monika; Martyna, Aleksandra; Czernik, Sławomir; Tokarska-Rodak, Małgorzata; Chwedczuk, Marta; Foll-Josselin, Béatrice; Ruchaud, Sandrine; Bach, Stéphane; Demchuk, Oleg M.; Kubiński, Konrad
    Small molecules containing quinone and/or oxime moieties have been found as promising anti-fungal agents. One of them is 4-AN, a recently reported potent anti-Candida compound, which inhibits the formation of hyphae, decreases the level of cellular phosphoproteome, and finally shows no toxicity towards human erythrocytes and zebrafish embryos. Here, further research on 4-AN is presented. The results revealed that the compound: (i) Kills Candida clinical isolates, including these with developed antibiotic resistance, (ii) affects mature biofilm, and (iii) moderately disrupts membrane permeability. Atomic force microscopy studies revealed a slight influence of 4-AN on the cell surface architecture. 4-AN was also shown to inhibit multiple various protein kinases, a characteristic shared by most of the ATP-competitive inhibitors. The presented compound can be used in novel strategies in the fight against candidiasis, and reversible protein phosphorylation should be taken into consideration as a target in designing these strategies.