Nifuroxazide
 | |
| Clinical data | |
|---|---|
| AHFS/Drugs.com | International Drug Names |
| Routes of administration | Oral |
| ATC code | |
| Identifiers | |
IUPAC name
| |
| CAS Number | |
| PubChem CID | |
| DrugBank | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEMBL | |
| CompTox Dashboard (EPA) | |
| ECHA InfoCard | 100.012.293 |
| Chemical and physical data | |
| Formula | C12H9N3O5 |
| Molar mass | 275.220 g·mol−1 |
| 3D model (JSmol) | |
SMILES
| |
InChI
| |
  (what is this?) (verify) | |
Nifuroxazide (INN) is an oral nitrofuran antibiotic, patented since 1966[1] and used to treat colitis and diarrhea in humans and non-humans.[2] It is sold under the brand names Ambatrol, Antinal, Bacifurane, Diafuryl (Turkey), Benol (Pakistan), Pérabacticel (France), Antinal, Diax (Egypt), Dearexin (Guatemala), Nifrozid, Ercefuryl (Romania, Czech Republic, Russia), Erfuzide (Thailand), Endiex (Slovakia), Enterofuryl (Bosnia and Herzegovina, Montenegro, Russia), Pentofuryl (Germany), Nifuroksazyd Hasco, Nifuroksazyd Polpharma (Poland), Topron, Enterovid (Latin America), Eskapar (Mexico), Enterocolin, Terracolin (Bolivia), Apazid (Morocco), Nifroxid (Tunisia), Hufafural, Nifural (Indonesia), Nitronal (Georgia) and Septidiaryl. It is sold in capsule form and also as a suspension.
Medical uses
Nifuroxazide have been found effective in infective diarrhea.[3]
Mechanism of action
Nifuroxazide is a nitrofuran antibacterial used for acute infectious diarrhea and related gastrointestinal infections; it is designed to act locally in the gut rather than systemically. Systemic absorption is negligible at therapeutic doses. Action of the drug is confined to the intestinal lumen, making it suitable for diarrheal infections where a local effect is desired.
The nitro group of nifuroxazide is reduced by bacterial nitroreductases, generating reactive species that disrupt essential bacterial enzymes and macromolecules, so that the net effect is bactericidal activity localized to the gut lumen.
History
Maurice Claude Ernest Carron patented the drug in the United States in 1966.[1] Subsequent patents issued to Germano Cagliero of Marxer S.p.A. describe the use of nifuroxazide as an antibiotic used to treat livestock.[2]
Health claims
In 1997, in an Ivory Coast promotional leaflet, GlaxoSmithKline claimed that nifuroxazide (under the brand name "Ambatrol") is an anti-dehydration treatment, "neutralise[s] microbacterials" in diarrhoea, and has "a spectrum which covers most enteropathogenic microbacterials, Shigella, Escherichia coli, Salmonella, Staphylococci, Klebsiella, Yersinia".[4] The international non-profit organization Healthy Skepticism, at the time using their former name, Medical Lobby for Appropriate Marketing (MaLAM), disagreed, stating "We have not found any scientific evidence to support these claims."[4]
Research directions
STAT3 inhibition
In addition to its antibiotic activity, nifuroxazide has been predicted to possess properties of inhibiting STAT3, so it can potentially interfere with a specific cell signaling pathway that some cancer cells depend on for survival, proliferation, and metastasis.[5][6]
ALDH1 cancer stem cells
Nifuroxazide was found to be bio-activated by ALDH1 enzymes, and can potentially kill ALDH1-High melanoma cells in experimental human cell systems and mouse models. High aldehyde dehydrogenase (ALDH) 1 enzymatic activity is a marker for cancer stem cell/tumour initiating cell populations in some cancers. ALDH1 is enriched in melanoma patient samples following BRAF and MEK inhibitor treatments, and it has been proposed that nifuroxazide may be researched in this context.[7] [5][6]
USP21 inhibition
Recent preclinical studies suggest that nifuroxazide can potentially inhibit USP21, a deubiquitinase implicated in cancer progression, by suppressing its enzymatic activity and reducing the expression of specific microRNAs that regulate USP21, but the solid evidence on potential applications is lacking.[8][9]
References
- 1 2 US 3290213, Carron MC, "Antibacterial nitrofurfurylidene derivatives and methods of using same", issued 6 December 1966, assigned to Laboratories Robert et Carriere SA
- 1 2 US 4093746, Cagliero G, "Method of and fodder for rearing white-meat calves for slaughter", issued 6 June 1978, assigned to Marxer SpA
- ↑ Scarpignato C, Rampal P (1995). "Prevention and treatment of traveler's diarrhea: a clinical pharmacological approach". Chemotherapy. 41 Suppl 1: 48–81. doi:10.1159/000239397. PMID 7671647.
- 1 2 "SmithKline Beecham Ambatrol (nifuroxazide)". Healthy Skepticism. June 1997. Archived from the original on 2010-12-31. Retrieved 2010-12-21.
- 1 2 Bailly C (September 2019). "Toward a repositioning of the antibacterial drug nifuroxazide for cancer treatment". Drug Discovery Today. 24 (9): 1930–1936. doi:10.1016/j.drudis.2019.06.017. PMID 31260646. S2CID 195771445.
- 1 2 Althagafy HS, El-Aziz MK, Ibrahim IM, Abd-Alhameed EK, Hassanein EH (July 2023). "Pharmacological updates of nifuroxazide: Promising preclinical effects and the underlying molecular mechanisms". Eur J Pharmacol. 951 175776. doi:10.1016/j.ejphar.2023.175776. PMID 37192715.
- ↑ Sarvi S (December 2018). "ALDH1 Bio-activates Nifuroxazide to Eradicate ALDH High Melanoma-Initiating Cells". Cell Chemical Biology. 25 (12): 1456–1469. doi:10.1016/j.chembiol.2018.09.005. PMC 6309505. PMID 30293938.
- ↑ Tak J, Nguyen TK, Lee K, Kim SG, Ahn HC (May 2024). "Utilizing machine learning to identify nifuroxazide as an inhibitor of ubiquitin-specific protease 21 in a drug repositioning strategy". Biomed Pharmacother. 174 116459. doi:10.1016/j.biopha.2024.116459. PMID 38518599.
- ↑ Liu L, Ma C, Ji J, Gao R, Li D (June 2025). "Role of antidiarrheal agents nifuroxazide in antitumor multi‑target anticancer, multi‑mechanism anticancer drug (Review)". Oncol Lett. 29 (6): 260. doi:10.3892/ol.2025.15006. PMC 11995686. PMID 40230426.