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Information × Registration Number 0224U032915, (0124U002114) , R & D reports Title Novel synthetic nitrogen-containing heterocyclic compounds with antimicrobial and anti-cancer activity popup.stage_title Синтез та дослідження похідних імідазолу, морфоліну та фосфорильованих похідних оксазолу як нових антимікробних та протиракових агентів Head Hodyna Diana M., к.б.н. Registration Date 11-12-2024 Organization V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine popup.description1 Design and experimental analysis of new biologically active low molecular weight chemical compounds among nitrogen-containing heterocycles using in silico, in vitro and in vivo methods as potential antibacterial, antifungal and anticancer agents with a specific molecular mechanism of action. Determination of antioxidant potential and toxicity of identified promising imidazole, morpholine and oxazole derivatives. popup.description2 Based on the developed QSAR models with high stability and predictive ability for the analysis and selection of new potential inhibitors of bacterial and fungal pathogens, a number of promising phosphorylated oxazole derivatives, lysosomotropic detergents based on imidazole and morpholine derivatives containing both dodecyl radicals and ester-functionalized long alkyl chains were identified and synthesized. Potentially active compounds were synthesized and characterized using IR, 1H, 13C, 31P NMR spectroscopy and chromatography-mass spectrometry, and studied in vitro and in vivo. In vitro studies of synthesized compounds with predicted high activity confirmed the perfection of the created predictive models and allowed to recommend some imidazole, morpholine and phosphorylated oxazole derivatives as new promising antimicrobial (against a wide range of bacterial cultures, such as Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, Staphylococcus aureus, and fungi of the genus Candida, including antibiotic-resistant clinical isolated strains) and anticancer (against the human laryngeal cancer cell line HEp-2) agents with high potential cytotoxic activity. The obtained in silico results of the antifungal mechanism of action of imidazole and morpholine derivatives by the molecular docking method allowed to propose the lanosterol 14α-demethylase as a potential biotarget. Phosphorylated oxazole derivatives showed the best affinity for bacterial enoyl-ACP reductase, the activity of which is a key factor in type II fatty acids synthesis. It was found that almost all the studied compounds have pronounced antioxidant properties, in some cases exceeding the free radical oxidation of lipids of the known antioxidant ionol by 2 times. The results of toxicological studies of promising compounds on the biomodel Daphnia magna as a known biosensor showed that the compounds belong to the class of highly and moderately toxic substances. Product Description popup.authors Kachaieva Maryna V. Severin Oleksandr O. Shulha Yurii V. popup.nrat_date 2024-12-11 Close