Danofloxacin is a broad-spectrum antibiotic and third-generation fluoroquinolone class. It was developed by Pfizer and is a synthetic analog of ciprofloxacin. It was introduced in 1991 for pathogens that cause respiratory diseases of bovine, swine and poultry. Danofloxacin inhibits Exosome component 10 (EXOSC10), a protein encoded by the EXOSC10 gene which is involved in RNA processing. Thus, Danofloxacin can be used to study regulatory networks governing RNA stability/turnover.
Danofloxacin is slightly soluble in water.
| Mechanism of Action |
Like other fluoroquinolones, Danofloxacin inhibits bacterial DNA gyrase (topoisomerase II) which is essential for DNA replication. Therefore, it inhibits bacterial DNA synthesis and cell division. Danofloxacin is an EXOSC10 inhibitor which results in interference with RNA processing, leading to accumulation of RNA substrates that would normally be processed if not for this inhibition. |
| Spectrum |
Danofloxacin has broad-spectrum activity, including bactericidal activity against Gram-positive and Gram-negative bacteria. It has in vitro activity against various Mycoplasmas. It also has activity against intracellular pathogens like Chlamydia and Brucella species. |
| Microbiology Applications |
Danofloxacin is commonly used in clinical in vitro microbiological antimicrobial susceptibility tests (panels, discs, and MIC strips) against Gram-positive and Gram-negative microbial isolates. Medical microbiologists use AST results to recommend antibiotic treatment options. Representative MIC ranges include: Manheimia haemolytica: 0.015-0.125 ug/ml For a representative list of Danofloxacin MIC values, click here. Clinical breakpoint (CBP) of Danofloxacin against of Mycoplasma gallisepticum was evaluated and authors emphasized that its use should consider the MIC and the effect of the antibiotic on the respiratory microbiota. The causative mycoplasma makes many metabolites that cause dysfunction of the respiratory mucosal epithelial cells (Wang et al, 2022). Danofloxacin inhibits Exosome component 10 (EXOSC10), a protein encoded by the EXOSC10 gene. This gene is involved in RNA processing. The exosome plays a part in RNA homeostasis. Specifically, is has 3'-5' exonuclease activity which is needed for degrading RNA substrates. Thus, research using Danofloxacin is useful for studying the regulatory networks governing RNA stability/turnover. Analytical methods can be used to quantify Danofloxacin. The LC-DAD method (ie. Diodode Array Detector) can quantify the compound in the presence of its degradation products such that it can be used for stability studies. Microbiological assays cannot be used for quantification due to the biological activity of the photoproducts (Cordeiro et al, 2020). |
| Eukaryotic Cell Culture Applications |
Studies have shown that high concentrations of Danofloxacin display cytotoxic effects involving apoptosis and/or necrosis. It also induces a concentration-dependent increase in ROS production in renal tubular cells epithelial cell line (LLC-PK1)(Yu et al, 2013). |
| Cancer Applications |
A new derivative of Danofloxacin called LZ-101, developed for veterinary use, was investigated against non-small-cell lung carcinoma (NSCLC). In vitro, it inhibited the viability of human NSCLC cell lines. It induced mitochondrial-mediated apoptosis and stabilizes the transcription factor FOXO3a by blocking autophagy flux. Thus, LZ-101 has anti-tumor activity and could be a candidate for further studies (Guo et al, 2019). |
| Molecular Formula | C19H20FN3O3 |
| References |
Cooper AC, Fuller JR, Fuller MK, Whittlestone P and Wise DR (1993) In vitro activity of Danofloxacin, tylosin and oxytetraycline against mycoplasmas of veterinary importance. Res. Vet. Sci. 54(3):329-334 PMID 8393208 Cordeiro et al (2020) Validation of an analytical method by high-performance liquid chromatography and microbiological assay, biological safety and in silico toxicity for Danofloxacin. Braz. J. Pharm. Sci 56: e18355 Guo Y, Zhao Y, Zhou Y et al (2019) LZ-101, a novel derivative of Danofloxacin, induces mitochondrial apoptosis by stabilizing FOXO3a via blocking autophagy flux in NSCLC cells. Cell Death Dis. 10:484 PMID 31217472 Wang S et al (2022) Rational use of Danofloxacin for treatment of Mycoplasma gallisepticum in chickens based on the clinical breakpoint and lung microbiota shift. Antibiotics (Basel). 11(3):403 PMID 35326865 Yu CH (2013) Effect of Danofloxacin on reactive oxygen species production, lipid peroxidation and antioxidant enzyme activities in kidney tubular epithelial cell line, LLC-PK1. Basic Clin. Pharmacol. Toxicol. 113(6):377-384 PMID 23855763 |
