Originator
Ercefuryl,Carriere,France,1964
Manufacturing Process
13 g (0.1 mol) of 4-hydroxybenzhydrazide were dissolved in a boiling mixture
of 100 ml of water and an equal volume of dimethylformamide. 15.5 g (0.11
mol) of 5-nitrofurfural dissolved in 31 ml of dimethylformamide were added to
this hot solution, and the mixture was stirred and brought to the boiling point.
The mixture was then allowed to stand for fifteen hours. The precipitate was
separated, washed twice with 100 ml of water, and recrystallized by dissolving
it in 250 ml of hot pyridine and pouring this solution into 250 ml of water.
The 5-nitrofurfurylidene hydrazide of 4-hydroxybenzoic acid obtained was
washed with water and methanol and was dried at a moderate temperature. It
weighed 23 g (83.7% yield), and melted at 298°C. The percentage nitrogen
determined by the micro-Dumas method was 15.41% (theory 15.27%).
Biological Activity
Nifuroxazide is a nitrofuran antibiotic. It is active against strains of the enteropathogenic bacteria C. jejuni, Salmonella, Y. enterocolitica, Shigella, and E. coli. It inhibits quorum sensing and virulence factor production in P. aeruginosa. Nifuroxazide inhibits STAT3 activity in a reporter assay (IC50 = ~3 μM) and decreases viability of U266 and INA-6 myeloma cells, which have constitutive STAT3 phosphorylation, with EC50 values of approximately 4.5 μM for both. It also decreases viability, migration, and invasion of, and induces apoptosis in, MCF-7, 4T1, and MDA-MB-231 breast cancer cells. Nifuroxazide (50 mg/kg per day) reduces tumor growth and prevents pulmonary metastasis in a 4T1 murine mammary carcinoma model. It also reduces diarrhea, weight loss, and colon inflammation in a rat model of acetic acid-induced ulcerative colitis.
