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INSIGHTS INTO MYCOBACTERIAL ACTIVITY AND CYTOTOXICITY OF SUBSTITUED ISOXAZOLE-4-CARBOHYDRAZIDE DERIVATIVES.

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Płoszaj P., Junka A., Szponar B., Mączyński M., Ryng S., Bartoszewicz M., Piwowar A.
Acta Poloniae Pharmaceutica - Drug Research
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2018
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vol. 75
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issue 3
EN
The purpose of this study was to evaluate the antimycobacterial activity of novel derivatives of 5-amino-3-methyl-4-isoxazolecarboxylic acid hydrazide 1, isoniazid (INH) structural analogue. A set of 5-amino-3-methyl-4-isoxazolecarboxylic acid hydrazide 1 derivatives 2a-j have been obtained by condensation reactions with aldehydes and further transformed by cyclization with corresponding orthoesters to 5-amino-3-methylisoxazole[5,4-d]pyrimidin-4-one derivatives 3a-j and 4a-j. From the structural and functional point of view, all these products proved to be biologically important and could be used as substrates for further synthesis. 21 out of 31 structures were newly developed. Described compounds were screened against Mycobacterium fortuitum in MABA test. The most active compound 2e, 2g revealed minimum inhibitory concentration at 16 μg/ml. In addition, these compounds revealed low cytotoxicity against lung (A549) and fibroblasts (L929) cell lines. The results demonstrated the potential and importance of further development of 5-amino-3-methyl-4-isoxazolecarboxylic acid hydrazide derivatives as a new class of antimycobacterial compounds.
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Differences in metabolic profiles of planktonic and biofilm cells in Staphylococcus aureus - 1H Nuclear Magnetic Resonance search for candidate biomarkers

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Junka A., Deja S., Smutnicka D., Szymczyk P., Ziółkowski G., Bartoszewicz M., Młynarz P.
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2013
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vol. 60
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issue 4
701-706
EN
Staphylococcus aureus is responsible for many types of infections related to biofilm presence. As the early diagnostics remains the best option for prevention of biofilm infections, the aim of the work presented was to search for differences in metabolite patterns of S. aureus ATCC6538 biofilm vs. free-swimming S. aureus planktonic forms. For this purpose, Nuclear Magnetic Resonance (NMR) spectroscopy was applied. Data obtained were supported by means of Scanning Electron Microscopy, quantitative cultures and X-ray computed microtomography. Metabolic trends accompanying S. aureus biofilm formation were found using Principal Component Analysis (PCA). Levels of isoleucine, alanine and 2,3-butanediol were significantly higher in biofilm than in planktonic forms, whereas level of osmoprotectant glycine-betaine was significantly higher in planktonic forms of S. aureus. Results obtained may find future application in clinical diagnostics of S. aureus biofilm-related infections.
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