Antibacterial agents for the treatment of bacterial infections work on the principle of selective toxicity: they destroy pathogenic cells and have no effect on the host. Antibiotics are antibacterial agents of natural or semi-synthetic, while chemotherapeutics are of synthetic origin. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration describe the susceptibility of a bacterial strain to the drug. Extensive and excessive misuse of antibiotics and inadequate control of bacterial infections have led to the emergence of genetically and biochemically resistant bacteria, which pose a great danger to our health. Therefore, the search for and development of new antibacterial agents has become necessary.
In this master's thesis, we evaluated the antibacterial activity of various compounds, for which we determined the minimum inhibitory concentrations on the microtiter plates by the microdilution method. Flavonoids did not show significant activity on Escherichia coli (MIC > 0.25 mM), while FLAV-9 (MIC = 0.031 mM) had strong effect on Staphylococcus aureus. The activity of plant extracts was tested for bacteria and the yeast Candida albicans, on which the extracts showed no effect. St. John's wort extract (EK-17) had the strongest effect on S. aureus with MIC ⡤ 3.91 μg/mL, and also had the strongest effect on the growth of multidrug-resistant MRSA. Among the β-lactam antibiotics tested, only imipenem showed an effect on E. coli (MIC = 1 μg/mL) and S. aureus (MIC = 0.5 μg/mL). Targeting and inhibiting bacterial efflux pumps are options to reduce the occurrence and spread of resistance. Among 9 tested efflux pump inhibitors, carbonyl cyanide m-chlorophenyl hydrazone (EPI-7) had the strongest effect on the tested bacterium. Filamentous temperature-sensitive protein Z (FtsZ) is a highly conserved bacterial protein with an important role in cell division. The protein inhibitors were variously substituted heterocycles, which mostly contained 1,4-benzodioxane linked via a methyleneoxy bridge to 2,6-difluorobenzamide. FZ100 and FZ95 inhibitors showed strong activity on S. aureus and MRSAs. A potential combination of efflux pump inhibitors and FtsZ protein inhibitors as a therapeutic option for the treatment of bacterial infections was evaluated by a checkerboard test on microtiter plates. The calculated values of the fractional inhibitory concentration index corresponded to the range 0.5 – 4 (indifference). This means that the inhibitors do not act synergistically, have no effect on each other and their combined effect is as great as the effect of an individual inhibitor.
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