Design, Synthesis, and Evaluation of Novel Tyrosine ‐Based DNA Gyrase B Inhibitors

The discovery and synthesis of new tyrosine‐based inhibitors of DNA gyrase B (GyrB), which target its ATPase subunit, is reported. Twenty‐four compounds were synthesized and evaluated for activity against DNA gyrase and DNA topoisomerase IV. The antibacterial properties of selected GyrB inhibitors were demonstrated by their activity against Staphylococcus aureus and Enterococcus faecalis in the low micromolar range. The most promising compounds, 8a and 13e, inhibited Escherichia coli and S. aureus GyrB with IC50 values of 40 and 30 µM. The same compound also inhibited the growth of S. aureus and E. faecalis with minimal inhibitory concentrations (MIC90) of 14 and 28 µg/mL, respectively. A series of novel tyrosine‐based inhibitors of DNA gyrase B (GyrB) were designed, synthesized, and evaluated against DNA gyrase and DNA topoisomerase IV. Compounds 8a and 13e, which inhibited E. coli and S. aureus GyrB and displayed inhibitory activity against the growth of S. aureus and E. faecalis were identified as promising compounds for further structural optimization.
Source: Archiv der Pharmazie - Category: Drugs & Pharmacology Authors: Tags: Full Paper Source Type: research