5-Fluorocytosine

- Overview
  - 5-Fluorocytosine (syn. Flucytosine) is a fluorinated cytosine (pyrimidine) analog with antifungal activity. First developed in 1957, it is active against Candida and Cryptococcus and is a competitive inhibitor of uracil metabolism. 5-Fluorocytosine is taken up by the fungus and is converted to the cytostatic 5-fluorouracil by cytosine deaminase. 5-Fluorocytosine can also be used in brain tumor research models using the virus Toca 511 which codes for cytosine deaminase. 5-Fluorocytosine is sparingly soluble in water.
    
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    Background
    
    5-Fluorocytosine is taken up by the fungus and is deaminated by cytosine deaminase (CD) and converted to the cytostatic 5-fluorouracil (5-FU). During transcription, the pyrimidine analog is incorporated into the RNA which inhibits subsequent rounds of transcription and building of certain essential proteins.
    An additional mechanism of action involves the conversion of 5-Fluorocytosine to 5-fluorodeoxyuridinemonophosphate, which inhibits fungal DNA synthesis.
- Properties
  - CAS Number
    
    2022-85-7
    
    Molecular Formula
    
    C4H4FN3O
    
    Molecular Weight
    
    129.09
    
    Appearance
    
    White or almost white crystalline powder
    
    Solubility
    
    Sparingly soluble in water (10.5 mg/mL). Slightly soluble in alcohol.
    
    Other Properties
    
    Source: Synthetic
    Assay: 98.5-101.0% (on dried basis)
    Residue On Ignition: ≤0.1%
    Heavy Metals: ≤0.002%
    Loss on Drying: ≤1.5%
    Purity Level: ≥98.5% (on dried basis)
    
    Storage
    
    2-8°C; Protect from light.
    
    * For research use only
- Applications
  - Application Description
    
    Spectrum: 5-Fluorocytosine is active in vitro and in vivo against some strains of Candida and Cyptococcus species.
    
    Microbiology Applications: 5-Fluorocytosine was found to be very active in vitro in a study with 8803 Candida isolates representing 18 yeast species (8803 isolates) using broth microdilution testing, with 95% of the isolates being susceptible. The compound had a prolonged post-antifungal effect and concentration-independent activity (Pfaller et al, 2002).
    In a study of over 1000 isolates of Candida exposed to 5-Fluorocytosine, 83.4% of them were susceptible. Resistance was uncommon (10.4% of isolates) and an MIC > 32 µg/ml was an indication of resistance in vitro (Quindós et al, 2004).
    Representative MIC data for 5-Fluorocytosine is available from our Antimicrobial Index.
    
    Plant Biology Applications: 5-Fluorocytosine can be used as a negative selection agent in transgenic plants using a bacterial cytosine deaminase codA gene in tobacco plant systems. In transformed callus, expression of this gene results in cell death on 5-Fluorocytosine (Stougaard et al, 1993).
    
    Cancer Applications: 5-Fluorocytosine can be used in gene therapy applications in mouse models of brain cancer. Researchers used replicating virus Toca 511 that infects dividing cells, preferentially malignant cells. The virus encodes an optimized yeast-derived cytosine deaminase (CD) that converts 5-Fluorocytosine into 5-fluorouracil (5-FU) which selectively kills dividing cells. This allows infected cells to remain as a reservoir of virus capable of infecting new malignant cells during subsequent viral proliferation. Authors used 2 immunocompetent mouse brain tumor models (CT26 in BALB/c mice and Tu-2449 in B6C3F1 mice) to show that the conversion proceeded in vivo. Repeated cycles of 5-FC administration was able to shrink and prevent further growth of the IC tumor (Ostertag et al, 2012).