Nifuroxazide
[CAS# 965-52-6]

Identification

• Classification: API >> Antibiotics >> Other antibiotics
• Name: Nifuroxazide
• Synonyms: p-Hydroxybenzoic acid (5-nitrofurfurylidene) hydrazide
• Molecular Formula: C₁₂H₉N₃O₅
• Molecular Weight: 275.22
• CAS Registry Number: 965-52-6
• EC Number: 213-522-0
• SMILES: C1=CC(=CC=C1C(=O)N/N=C/C2=CC=C(O2)[N+](=O)[O-])O

Properties

• Density: 1.5±0.1 g/cm³ Calc.^*
• Index of refraction: 1.653 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H312-H332
• Precautionary Statements: P261-P264-P270-P271-P280-P301+P317-P302+P352-P304+P340-P317-P321-P330-P362+P364-P501

Discovory and Applicatios

Nifuroxazide is a nitrofuran derivative with established antimicrobial activity, primarily used as an intestinal antiseptic. It is classified chemically as 4-hydroxy-N′-\[(5-nitrofuran-2-yl)methylene]benzohydrazide. The compound contains a nitrofuran ring, which is a key pharmacophore in several antimicrobial agents, and a hydrazone linkage to a substituted benzohydrazide group.

Nifuroxazide was first synthesized in the mid-20th century during efforts to develop synthetic antibiotics with local action in the gastrointestinal tract and minimal systemic absorption. Its design focused on exploiting the antimicrobial properties of the nitrofuran moiety while minimizing systemic exposure to reduce side effects. The synthesis involves the condensation of 5-nitrofurfural with 4-hydroxybenzohydrazide under mild conditions to form the Schiff base linkage that characterizes the molecule.

Chemically, nifuroxazide is a yellow crystalline powder, practically insoluble in water but soluble in ethanol, acetone, and other organic solvents. Its stability under normal storage conditions makes it suitable for oral pharmaceutical formulations, especially tablets and suspensions. The nitro group on the furan ring is essential for its antibacterial activity, and the presence of the hydrazone linkage plays a role in the compound's selective reactivity and pharmacokinetic properties.

Pharmacologically, nifuroxazide acts by interfering with bacterial enzyme systems, particularly those involved in electron transport and redox cycling, leading to disruption of bacterial metabolism and growth. It is active against a broad spectrum of Gram-positive and Gram-negative bacteria that cause intestinal infections, such as *Escherichia coli*, *Salmonella spp.*, and *Shigella spp.* However, it is not systemically absorbed in significant amounts, which limits its use to infections localized in the gastrointestinal tract.

Clinically, nifuroxazide has been used to treat acute diarrhea of bacterial origin and other infectious gastrointestinal disorders. Its main advantage is the low systemic absorption, which allows for effective treatment with a minimal risk of systemic toxicity or bacterial resistance outside the gut. Because it is not absorbed, it also does not disturb systemic flora or produce effects on distant organs.

Nifuroxazide has also been studied for other potential applications. More recent research has investigated its effects on inflammatory pathways and as a possible modulator of STAT3 signaling, although these investigations remain experimental and are not part of established medical practice. Its role in the treatment of multidrug-resistant bacterial strains and possible applications in oncology are under early-stage investigation but are not part of its approved uses.

Analytical methods for quality control and detection of nifuroxazide in pharmaceutical formulations include high-performance liquid chromatography (HPLC), ultraviolet-visible (UV-Vis) spectrophotometry, and infrared (IR) spectroscopy. These methods allow confirmation of identity, purity, and concentration in dosage forms. The compound exhibits characteristic IR bands associated with the nitro group and hydrazone moiety, and distinct UV absorption due to the conjugated furan system.

Physically, nifuroxazide is stable when stored in sealed containers away from moisture and light. It is generally well tolerated, though mild gastrointestinal disturbances may occur. Because it is not absorbed systemically, the risk of systemic side effects is minimal. It is not used in parenteral or intravenous forms and is restricted to oral administration.

In summary, nifuroxazide is a nitrofuran-based antibacterial agent developed for the treatment of gastrointestinal infections. Its lack of systemic absorption, chemical stability, and targeted antimicrobial action have made it a widely used intestinal antiseptic in several countries. Its therapeutic relevance remains mainly in the domain of gastroenterology, supported by decades of clinical use.

References

2024. Utilizing machine learning to identify nifuroxazide as an inhibitor of ubiquitin-specific protease 21 in a drug repositioning strategy. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 174.
DOI: 10.1016/j.biopha.2024.116459

2023. Nifuroxazide attenuates indomethacin-induced renal injury by upregulating Nrf2/HO-1 and cytoglobin and suppressing NADPH-oxidase, NF-κB, and JAK-1/STAT3 signals. Naunyn-Schmiedeberg's Archives of Pharmacology, 397(6).
DOI: 10.1007/s00210-023-02851-5

1981. Evaluation of the in Vitro Activity of Nifuroxazide on Enteropathogenic Microorganisms: Determination of Bacteriostatic and Bactericidal Concentrations and Disk Susceptibility. Acta Clinica Belgica, 36(4).
DOI: 10.1080/22953337.1981.11718797