Antimicrobial activity of selected heterocyclic organic compounds from the FCCT compound libraryRažnjević, Nives (Avtor) Novinec, Marko (Mentor) Bacterial InfectionsDrug ResistanceAnti-Bacterial CompoundsChemical SynthesisThe development of antibiotic-resistant strains of bacteria poses a real threat and burden to the healthcare system. In this master thesis, 100 different compounds available in the compound library of the Chair of Biochemistry and the Chair of Organic Chemistry UL FCCT were tested for bacterial growth inhibition on four bacterial species - Staphylococcus aureus, Bacillus thuringiensis, Escherichia coli, and Pseudomonas aeruginosa. Growth inhibition was monitored spectrophotometrically. All compounds were tested at a concentration of 100 µg/mL. Inhibition was confirmed by testing using a modified Kirby-Bauer disk diffusion method with the disks impregnated with 20 µg of the respective compound. The presence of the inhibition zone was considered as confirmation of inhibitory activity. After the inhibitory activity was confirmed, the minimum inhibitory concentration was determined. Among the tested compounds, 9 compounds showed antimicrobial activity, out of which two were further characterized. 2-[(4-chloro-1-hydroxynaphthalene-2-carbonyl)amino]-2-methylpropanoic acid (compound 1) showed selective antimicrobial effect only on S. aureus with a minimum inhibitory concentration of 125 µg/mL, while piperidyn-2-yl-{2-(trifluoromethyl)-6-[4-(trifluoromethyl) phenyl] pyridin-4-yl}methanol (compound 2) inhibited the growth of all strains tested. The minimum inhibitory concentration of compound 2 for S. aureus and B. thuringiensis was 88 µg/mL, for E. coli 175 µg/mL, and for P. aeruginosa 316 µg/mL. Growth dynamics was monitored for compound 2 and compared with non-treated cells over 6 hours. During the observed period, there was no increase in bacterial concentration in the presence of the test compound. Compound 1 proved to be interesting due to its selective inhibitory activity. The analogs of the reactants for the compound 1 synthesis were readily available at the Chair of Organic Chemistry FCCT and were used to synthesize an analog of compound 1, which was designated as compound 8. After synthesis, the structure and purity of the synthesized analog were verified. NMR spectroscopy showed that 287 mg of the pure compound was synthesized and was visible as a yellow powder. Then, the inhibitory activity of compound 8 was investigated. It was found to slightly inhibit the growth of all tested strains; however, the inhibition was less than 50% compared to the negative control. In parallel, we also tested the reactants used in the synthesis of compound 8, i.e. 2-hydroxy-1-naphthoic acid (HNA) and 2-amino-2-methylpropanoic acid methyl ester. Interestingly, HNA showed significant inhibitory activity (> 90%) on S. aureus and E. coli. Together, these results open novel possibilities in the discovery of antibacterials.20222022-01-26 14:25:01Magistrsko delo/naloga134696sl