Zoliflodacin

Zoliflodacin (formerly ETX-0914; AZD-0914; ETX0914; AZD0914) is a novel and potent spiropyrimidinetrione-based bacterial DNA gyrase/topoisomerase inhibitor. Zoliflodacin exhibits strong in vitro antibacterial activity against both Gram-positive and Gram-negative bacteria, including S. aureus with the MIC90 of 0.25 μg/mL. With regard to important Gram-positive (Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, and Streptococcus agalactiae), fastidious Gram-negative (Haemophilus influenzae and Neisseria gonorrhoeae), atypical (Legionella pneumophila), and anaerobic (Clostridium difficile) bacterial species, including isolates with documented fluoroquinolone resistance, AZD0914 exhibits strong in vitro antibacterial activity. In contrast to other commercially available antibacterial compounds, AZD0914 inhibits DNA biosynthesis and the accumulation of double-strand cleavages. Under permissive conditions, AZD0914 stabilizes and arrests the cleaved covalent complex of gyrase with double-strand broken DNA, preventing the double-strand cleaved DNA from religating to form fused circular DNA. This mechanism is different in terms of mechanics even though it is comparable to that of fluoroquinolones. In S. aureus, AZD0914 showed low frequencies of spontaneous resistance; if mutants were obtained, they mapped to gyrB. Furthermore, AZD0914 did not exhibit any cross-resistance against recent clinical isolates of bacteria that were resistant to fluoroquinolones or other drug classes, such as glycopeptides, β-lactams, macrolides, and oxazolidinones. In vitro time-kill studies and minimum bactericidal concentration tests, AZD0914 demonstrated bactericidal activity. Only additivity or indifference was seen in in vitro checkerboard/synergy testing using 17 comparator antibacterials. AZD0914's low frequency of resistance, lack of cross-resistance, strong in vitro antibacterial activity (including activity against isolates resistant to fluoroquinolones), and bactericidal activity all contribute to its continued development.

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.