Cell lines

P. aeruginosa Strains

Preparation method

The solubility of this compound in DMSO is >6.4mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

1, 4, 11, 33 and 100 μM; 14 h

Applications

In P. aeruginosa strains, 5-Flucytosine (5-FC) inhibited pyoverdine synthesis and pvdE transcription. In a P. aeruginosa PAO1 fur mutant, 5-Flucytosine also inhibited pyoverdine production, suggesting that 5-FC could repress iron uptake genes through a Fur-independent mechanism. 5-Flucytosine down-regulated the expression of toxA and prpL genes, which was consistent with the strongly reduced ToxA and PrpL levels in culture supernatants, two major virulence factors of P. aeruginosa.

Animal models

mouse model of pulmonary infection; mice infected with an isogenic pvdS mutant

Dosage form

30 mg/kg per day; i.p.

Application

In a mouse model of pulmonary infection with P. aeruginosa, 5-FC almost completely protected mice from the P. aeruginosa lethal challenge. All mice infected with the pvdS mutant survived the challenge, suggesting the importance of PvdS as a major pathogenicity determinant in P. aeruginosa pulmonary infection. 5-FC also reduced lesions and inflammation in bronchi and pulmonary parenchyma.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

Flucytosine (5-Fluorocytosine, 5-FC, Ancobon), a fluorinated pyrimidine analogue, is an antifungal drug.Target: antifungalFlucytosine, or 5-fluorocytosine, a fluorinated pyrimidine analogue, is a synthetic antimycotic drug. It is structurally related to the cytostatic fluorouracil and to floxuridine. It is available in oral and in some countries also in injectable form. A common brand name is Ancobon. Flucytosine was first synthesized in 1957 but its antifungal properties were discovered in 1964. The drug is dispensed in capsules of 250 mg and 500 mg strength. The injectable form is diluted in 250 mL saline solution to contain 2.5 g total (10 mg/mL). The solution is physically incompatible with other drugs including amphotericin B.Flucytosine is well absorbed (75 to 90%) from the gastrointestinal tract. Intake with meals slows the absorption, but does not decrease the amount absorbed. Following an oral dose of 2 grams peak serum levels are reached after approximately 6 hours. The time to peak level decreases with continued therapy. After 4 days peak levels are measured after 2 hours. The drug is eliminated renally. In normal patients flucytosine has reportedly a half-life of 2.5 to 6 hours. In patients with impaired renal function higher serum levels are seen and the drug tends to cumulate in these patients. The drug is mainly excreted unchanged in the urine (90% of an oral dose) and only traces are metabolized and excreted in the feces. Therapeutic serum levels range from 25 to 100 g/ml. Serum levels in excess of 100 ug are associated with a higher incidence of side effects. Periodic measurements of serum levels are recommended for all patients and are a must in patients with renal damage.

References:
[1]. Vermes A, et al. Flucytosine: a review of its pharmacology, clinical indications, pharmacokinetics, toxicity and drug interactions. J Antimicrob Chemother. 2000 Aug;46(2):171-9.
[2]. Te Dorsthorst DT, et al. In vitro interaction of flucytosine combined with amphotericin B or fluconazole against thirty-five yeast isolates determined by both the fractional inhibitory concentration index and the response surface approach. Antimicrob Agents Chemother. 2002 Sep;46(9):2982-9.