Zoliflodacin is a spiropyrimidinetrione antibiotic belonging to the fluoroquinolone class. It is a bacterial DNA gyrase inhibitor with in vitro antibacterial activity against key Gram-positive, fastidious Gram-negative, atypical bacteria, and anaerobic bacteria. It is used in gonorrhea research studies. Zoliflodacin was initially developed by Entasis Therapeutics, a spin-off of AstraZeneca.
Zoliflodain is freely soluble in DMSO.
| Molecular Formula | C22H22FN5O7 |
| Mechanism of Action | Zoliflodacin is a bacterial DNA gyrase inhibitor. Specifically, it stabilizes and stops the cleaved complex of DNA gyrase and thus blocks re-ligation of the double-stranded (dsDNA) cleaved DNA to form fused circular DNA. This results in inhibition of DNA biosynthesis and the accumulation of double-strand cleavages. |
| Spectrum | Zoliflodacin has activity against Gram-positive, Gram-negative, and atypical bacteria. |
| Microbiology Applications |
Zoliflodacin has in vitro activity against Gram-positive (Staphylococcus and Streptococcus sp.), fastidious Gram-negative species (Haemophilus influenzae, Neisseria gonorrhoeae), atypical bacteria (Legionella pneumophila), and anaerobic bacteria (Clostridium difficile). It also has activity against isolates with known resistance to fluoroquinolones. The compound has a low frequency of resistance, and there is a lack of cross-resistance seen. In vitro susceptibility of Zoliflodacin to 986 Neisseria gonorrhoeae isolates were tested with the agar dilution method. Mutations in the gyrA, gyrB, parC, parE, and mtrR genes were determined by PCR and sequencing. MICs ranged from ≤0.002 to 0.25 mg/L. Zoliflodacin had excellent in vitro activity against clinical gonococcal isolates, including those with high-level resistance to ciprofloxacin, azithromycin, and extended-spectrum cephalosporins (Le, 2021). Neisseria gonorrhoeae has been steadily developing high-level resistance to a wide range of antibiotic classes. The emergence of MDR N. gonorrhoeae strains is caused by many factors. Additionally, the bacterium has a natural competence for transformation. Gonococci can also acquire exogenous DNA from other Neisseriae, thus incorporating foreign genetic material into their own genome (Raccagni et al, 2023). |
| References |
Huband MD et al (2015) In vitro antibacterial activity of AZD0914, a new spiropyrimidinetrione DNA gyrase/topoisomerase inhibitor with potent activity against Gram-positive, fastidious Gram-negative, and atypical bacteria. Antimicrob Agents Chemother. 59(1):467-474 PMID 25385112 Le W (2021) Susceptibility trends of Zoliflodacin against multidrug-resistant Neisseria gonorrhoeae clinical isolates in Nanjing, China, 2014 to 2018. Antimicrob Agents Chemother 65:10.1128/aac.00863-20 Raccagni AR et al (2023) Neisseria gonorrhoeae antimicrobial resistance: The future of antibiotic therapy. J. Clin. Med. 2(24):7767 |