Nifuroxazide

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), 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), Nifural (Indonesia) and Septidiaryl. It is sold in capsule form and also as a suspension.

Nifuroxazide

Clinical data
AHFS/Drugs.com	International Drug Names
Routes of administration	Oral
ATC code	A07AX03 (WHO)
Identifiers
IUPAC name 4-hydroxy-N-[(E)-(5-nitrofuran-2-yl)methylideneamino]benzamide
CAS Number	965-52-6 N
PubChem CID	5337997
DrugBank	DB13855 Y
ChemSpider	4495115 Y
UNII	PM5LI0P38J
KEGG	D07111 Y
ChEMBL	ChEMBL244888 Y
CompTox Dashboard (EPA)	DTXSID4045343
ECHA InfoCard	100.012.293
Chemical and physical data
Formula	C12H9N3O5
Molar mass	275.220 g·mol−1
3D model (JSmol)	Interactive image
SMILES c1cc(O)ccc1C(=O)N/N=C/c2ccc(o2)[N+](=O)[O-]
InChI InChI=1S/C12H9N3O5/c16-9-3-1-8(2-4-9)12(17)14-13-7-10-5-6-11(20-10)15(18)19/h1-7,16H,(H,14,17)/b13-7+ Y Key:YCWSUKQGVSGXJO-NTUHNPAUSA-N Y
NY (what is this?)  (verify)

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]

Effectiveness in humans

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".^[3] 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."^[3]

STAT3 inhibition

In addition to its antibiotic activity, nifuroxazide has been found to be a potent inhibitor of STAT3, and consequently has been proposed as a cancer treatment.^[4]

ALDH1 cancer stem cells

High aldehyde dehydrogenase (ALDH) 1 enzymatic activity is a marker for cancer stem cell/tumour initiating cell populations in many cancers. Nifuroxazide was found to be bio-activated by ALDH1 enzymes, and shown to selectively kill ALDH1-High melanoma cells in experimental human cell systems and mouse models. ALDH1 is enriched in melanoma patient samples following BRAF and MEK inhibitor treatments, and it has been proposed that nifuroxazide may be useful as a cancer treatment in this context.^[5]

References

1. US 3290213, Carron MC, "Antibacterial nitrofurfurylidene derivatives and methods of using same", issued 6 December 1966, assigned to Laboratories Robert et Carriere SA
2. US 4093746, Cagliero G, "Method of and fodder for rearing white-meat calves for slaughter", issued 6 June 1978, assigned to Marxer SpA
3. "SmithKline Beecham Ambatrol (nifuroxazide)". Healthy Skepticism. June 1997. Archived from the original on 2010-12-31. Retrieved 2010-12-21.
4. 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.
5. 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.