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Information × Registration Number 0223U005003, 0122U002100 , R & D reports Title New antimicrobial heterocyclic compounds against multidrug-resistant bacterial strains: synthesis, in silico, in vitro studies popup.stage_title Head Hodyna Diana M., к.б.н. Registration Date 12-12-2023 Organization V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine popup.description2 Based on the formed databases of chemical compounds with antimicrobial properties by online platform OCHEM new qualitative classification and regression QSAR models with high stability and predictive ability were created for the analysis and selection of new potential inhibitors of bacterial pathogens among quinolone and pyrrole derivatives. Potentially bioactive trifluoromethylated bicyclic pyrroles and trifluoroacethyl-substituted quinolones identified based on QSAR prediction against several bacterial pathogens were synthesized, characterized by 1H, 19F, 13C NMR, and elemental analysis, and studied in vitro and in vivo. Conducted in vitro studies of synthesized compounds with predicted high activity confirmed the excellence of the created predictive models and made it possible to recommend some of new trifluoroacethyl-substituted quinolones and trifluoromethylated bicyclic pyrroles as promising antimicrobial agents against a wide range of gram-negative and gram-positive bacterial cultures, such as Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, and fungi Candida, including antibiotic-resistant clinical strains. The toxicological evaluation of promising compounds using the Daphnia magna hydrobiont as a known biosensor showed that tested compounds can be classified as moderately and slightly toxic substances according to the classification developed by Passino and Smith for hydrobionts. The obtained in silico results of the antibacterial and antifungal mechanism of action of trifluoromethylated bicyclic pyrroles by the molecular docking method allowed proposing bacterial enzymes, such as UDP-N-acetylenolpyruvylglucosamine reductase and lanosterol 14-α-demethylase, as relevant potential biotargets, while trifluoroacethyl-substituted quinolones can be targeted to bacterial DNA gyrase or topoisomerase IV. Product Description popup.authors Kachaieva Maryna V. Klipkov Аnton А. Shulga Yuriy V. popup.nrat_date 2023-12-12 Close