Browsing by Author "Masłyk, Maciej"

Now showing 1 - 5 of 5
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    A representative of arylcyanomethylenequinone oximes effectively inhibits growth and formation of hyphae in Candida albicans and influences the activity of protein kinases in vitro
    (Elsevier, 2018) Masłyk, Maciej; Janeczko, Monika; Demchuk, Oleg M.; Boguszewska-Czubara, Anna; Golczyk, Hieronim; Sierosławska, Anna; Rymuszka, Anna; Martyna, Aleksandra; Kubiński, Konrad
    In this study, we applied various assays to reveal new activities of phenylcyanomethylenequinone oxime-4-(hydroxyimino) cyclohexa-2,5-dien-1-ylidene](phenyl)ethanenitrile (4-AN) for potential anti-microbial applications. These assays demonstrated (a) the antimicrobial effect on bacterial and fungal cultures, (b) the effect on the in vitro activity of the kinase CK2, (c) toxicity towards human erythrocytes, the Caco-2 cancer cell line, and embryonic development of Zebrafish. We demonstrated the activity of 4-AN against selected bacteria and Candida spp. The MIC ranging from 4 µg/ml to 125 µg/ml proved effective in inhibition of formation of hyphae and cell aggregation in Candida, which was demonstrated at the cytological level. Noteworthy, 4-AN was found to inhibit the CK2 kinase with moderate potency. Moreover, at low concentrations, it did not exert any evident toxic effects on human erythrocytes, Caco-2 cells, or Zebrafish embryos. 4-AN can be a potential candidate as a novel drug against Candida infections.
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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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    New Supramolecular Drug Carriers: The Study of Organogel Conjugated Gold Nanoparticles
    (MDPI, 2021) Demchuk, Oleg M.; Kowalczuk, Joanna; Łapiński, Andrzej; Stolarczyk, Elżbieta; Kubiński, Konrad; Janeczko, Monika; Martyna, Aleksandra; Masłyk, Maciej; Turczyniak-Surdacka, Sylwia
    An aqueous solution of sodium citrate stabilized gold nanoparticles (AuNP) in the presence of N-lauroyl-L-alanine (C12ALA) forms a stable gel. The structure of the gel and the distribution profile of AuNP in it were analyzed. Will nanoparticles separated from each other with sodium citrate behave in the same way in solution and trapped in the gel matrix? Will the spatial limitation of solvent molecules aggregate nanoparticles and destroy their homogeneity? These questions are very important from the point of view of the use of gold nanoparticles, trapped in the gel structure, as carriers of drugs in the slow-release process. The lack of homogeneity of this distribution will have a major impact on the rate of release of the appropriate amount of therapeutic drug from the matrix. In this work, we attempt to answer these questions. The performed biological assays revealed that both C12ALA and C12ALA-AuNP show an excellent level of biological neutrality. They might be used as a transporting medium for a drug delivery without affecting the drug’s activity.
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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.
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    Vitamin B12-Enriched Yarrowia lipolytica Biomass Obtained from Biofuel Waste
    (Springer, 2020) Jach, Monika Elżbieta; Masłyk, Maciej; Juda, Marek; Sajnaga, Ewa; Malm, Anna
    The aim of the study was to obtain vitamin B12-enriched biomass of non-conventional yeast Yarrowia lipolytica A-101. The cultivations were performed on waste from biofuel production in aerobic conditions at different temperatures (20–30 °C) and pH values (4.0–7.0) of the medium, with and without the addition of cobalt, L-methionine, molybdenum, δ-aminolevulinic acid, and niacin. A temperature of 30 °C and pH between 5 and 6 were the optimal conditions for obtaining B12-enriched yeast biomass on biofuel waste. In such conditions, Y. lipolytica A-101 contained 9 µg of vitamin B12 per 100 g of dried biomass. The addition of the ingredients mentioned above to the medium did not exert a significant effect on the B12 concentration. Y. lipolytica are able to accumulate this vitamin from the medium in a similar manner to animal cells. Additionally, it should be noted that the dried biomass of Y. lipolytica appeared to be safe for consumption. Taken together, these data showed that Y. lipolytica can be used as a nutritional supplement to increase the intake of vitamin B12, especially at risk of vitamin B12 deficiency.