One of the biggest challenges humanity faces is the increasing resistance of bacteria to antibiotics. A very promising class of antibiotics is the so-called novel bacterial topoisomerase inhibitors (NBTI).
These new inhibitors are composed of three parts. The left part consists of heterocyclic compounds that intercalate between DNA base pairs. The right part is typically a halogenated aromatic ring, which forms a halogen bond with enzyme’s amino acid residues. The linker, which connects the left and right parts, comes in various forms.
As part of the master's thesis, we synthesised two molecules. We used two different spacers. The "left" part of the molecule was the same for both synthesised compounds. The "right" parts of the molecules differed in the substitution of the benzene ring. The product was isolated using chromatographic systems of different capacities. The structure of the molecules was confirmed through 1H and 13C spectra obtained by nuclear magnetic resonance and HRMS. We confirmed the biological activity through biological and enzymatic testing. The minimum inhibitory concentration (MIC), the concentration of the compound that inhibits bacterial growth, and residual enzyme activity were determined for both compounds. As expected, the compounds were more effective against Gram-positive bacteria than Gram-negative bacteria. Due to the small number of final compounds, we could not conclusively correlate the effectiveness of the compounds with the molecular structure, and could only make assumptions based on the results.
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