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Nitazoxanide

CAS No.55981-09-4
Chemical Name:Nitazoxanide
CBNumber:CB7219063
Molecular Formula:C12H9N3O5S
Formula Weight:307.28
MOL File:55981-09-4.mol

Nitazoxanide Property

Melting point 202°C
Density 1.629 g/cm3
storage temp. 2-8°C
solubility Soluble in DMSO (>50 mg/ml)
form solid
pka 6.18±0.50(Predicted)
color Off-white
λmax 416nm(Phosphate buffer sol.)(lit.)
Merck 14,6567
Stability Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
CAS DataBase Reference 55981-09-4(CAS DataBase Reference)
FDA UNII SOA12P041N
NCI Drug Dictionary nitazoxanide
ATC code P01AX11
UNSPSC Code 41116107
NACRES NA.77

Safety

Hazard Codes :Xn
Risk Statements :22-36/37/38
Safety Statements :26-36
WGK Germany :3
RTECS :VN7830000
HS Code :2934100000
Toxicity :LD50 orally in male, female mice: 1350, 1380 mg/kg; in rats: >10 g/kg (Murphy, Friedmann)

NFPA 704:

	0
2		0

Hazard and Precautionary Statements (GHS)

Symbol(GHS)
Signal wordWarning
Hazard statements H302-H315-H319-H335
Precautionary statements P264-P270-P280-P302+P352+P332+P313+P362+P364-P305+P351+P338+P337+P313-P501-P301+P312+P330-P305+P351+P338-P261

Nitazoxanide Price More Price(6)

Brand: Sigma-Aldrich(India)
Product number: N0290
Product name : Nitazoxanide
Purity: ≥98% (HPLC)
Packaging: 10MG
Price: ₹8746.6
Updated: 2022/06/14
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Brand: Sigma-Aldrich(India)
Product number: PHR2888
Product name : Nitazoxanide
Purity: pharmaceutical secondary standard, certified reference material
Packaging: 400MG
Price: ₹15382.33
Updated: 2022/06/14
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Brand: Sigma-Aldrich(India)
Product number: N0290
Product name : Nitazoxanide
Purity: ≥98% (HPLC)
Packaging: 50MG
Price: ₹31381.68
Updated: 2022/06/14
Buy: Buy

Brand: TCI Chemicals (India)
Product number: N1031
Product name : Nitazoxanide
Purity:
Packaging: 200MG
Price: ₹4300
Updated: 2022/05/26
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Brand: TCI Chemicals (India)
Product number: N1031
Product name : Nitazoxanide
Purity:
Packaging: 1G
Price: ₹10100
Updated: 2022/05/26
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Nitazoxanide Chemical Properties,Usage,Production

Description Nitazoxanide (NT Z) has been approved as an orphan drug for the treatment of diarrhea in children (age, 1–11 years) and is associated with giardiasis, but it also is approved for diarrhea caused by crytosporidiosis in patients with AIDS. Crytosporidiosis is a protozoal infection caused by Cryptosporidi um parvum. The condition is uncommon in healthy individuals but can be life-threatening in immunosuppressed patients and those with HIV infections.
Chemical Properties Crystalline Solid
Originator Alinia,Romark Laboratories, L.C.
Uses For the treatment of diarrhea in adults and children caused by the protozoa Giardia lamblia and for the treatment of diarrhea in children caused by the protozoa Cryptosporidium parvum.
Uses antihypertensive
Uses An anthelmintic (cestodes), antiprotozoal (cryptosporidium). Kills Mycobacterium tuberculosis.
Uses Nitazoxanide has been used:
- to test its anti-viral activity against chikungunya virus
- as an antiprotozoal agent to test its effect on cell viability in various cancer cell lines
- to test its effect on human cytomegalovirus (HCMV) infected human fibroblast HFF cells
Definition ChEBI: Acetic acid [2-[[(5-nitro-2-thiazolyl)amino]-oxomethyl]phenyl] ester is a carboxylic ester and a member of benzamides. It is functionally related to a salicylamide.
Manufacturing Process To a solution containing one mole p-metoxy-benzoyl chloride and one mole of carefully purified 2-amino-5-nitro-triazole in 200 ml of anhydrous tetrahydrofuran, one mole of triethylamine has been slowly added (about 10 minutes) while stirring. The reaction mixture, which became slightly warm, was stirred during 45 minutes and then poured under agitation, into 2 liters of distilled water. The stirring was continued until the precipitation of salicylamide, N-(5-nitro-2-thiazolyl)-, acetate (ester) was complete. The obtained precipitate was dried, washed with water, dried again and recrystallized from methanol. The yield about 60%; melting point 202°C.
brand name Alinia (Romark).
Therapeutic Function Anthelmintic
Antimicrobial activity In vitro Cryptosporidium parvum sporocytes and oocysts are inhibited by <33 μm, and Giardia lamblia (intestinalis) trophozoites by <10 μm. The metabolite tizoxanide is more active than the parent compound against some isolates. E. histolytica is inhibited by 6–23 μm (parent compound) and 5.6– 28 μm (metabolite), and T. vaginalis by 0.5–15.5 μm (parent compound) and 0.3–12.2 μm (metabolite). Activity against other micro- organisms, including some helminths, bacteria (Clostridium difficile) and viruses (hepatitis C) has also been demonstrated.
Acquired resistance Resistance caused by altered expression of genes involved in stress response has been demonstrated in experimental studies with G. lamblia.
General Description Nitazoxanide (NTZ), a thiazolide compound is a antiparasitic drug with structure similar to niclosamide.
Pharmaceutical Applications A synthetic broad-spectrum antiparasitic nitroheterocycle (2-acetyloxy- N-(5-nitro-2-thiazolyl) benzamide), formulated for oral use.
Biochem/physiol Actions Nitazoxanide is an inhibitor of pyruvate-ferredoxin oxidoreductase (PFOR); Antimicrobial recently found to kill both non-replicating and replicating mycobacteria. FDA approved anti-parasitic drug (2002). Recent work (C & EN Sept. 14, 2009, p. 28) highlights that NTZ kills non-replicating and replicating TB bacteria and no apparent resistance is detected.
Mechanism of action Nitazoxanide is a pro-drug that is metabolically converted into the deactylated drug tizoxanide (TIZ). The TIZ then undergoes a four-electron reduction of the 5-nitro group giving various short-lived intermediates, which may include the hydroxylamine derivative. It is these reduced products that represent the active form of NTZ. Whereas these intermediates would suggest that NTZ has the same mechanism of action as metronidazole, this does not appear to be the case. Nitazoxanide is thought to inhibit the enzyme pyruvate:ferredoxin oxidoreductase in Trichomonas vaginali s, Entamoeba histolytica, and Cl ostridium perfingens. The results of this inhibition is disruption of the bioenergetics of these organisms. Unlike metronidazole and tinidazole, which fragment DNA and are suspected mutagenic agents, NTZ and TIZ do not cause DNA fragmentation and are not considered to be mutagenic. This might be associated with the higher redox potential found for NTZ, a nitrothiazole, in comparison with very low redox potential found for the nitroimidazoles, such as metronidazole and tinidazole. Additional metabolites of TIZ also includes the glucuronide, which shows some biological activity, and small amounts of an aromatic hydroxylation product.
Pharmacokinetics After oral administration the major circulating metabolites are tizoxanide (desacetyl nitazoxanide) and its glucuronide. Minor metabolites include salicyluric acid and tizoxanide sulfate. Maximum concentrations of the active metabolites tizoxanide and tizoxanide glucuronide are observed within 1–4 h. Following a single oral dose of 500 mg given with food, the C_max of both metabolites was around 10 mg/L. Tizoxanide has a halflife of around 1–2 h and is >99.9% bound to plasma proteins.
Clinical Use It is indicated for the treatment of diarrhea caused by G. lamblia or C. parvum.
Side effects Nitazoxanide appears well tolerated. Side effects may include abdominal pain diarrhea, headache and nausea.
Veterinary Drugs and Treatments Nitazoxanide oral paste is indicated for the treatment of horses with equine protozoal myeloencephalitis (EPM) caused by Sarcocystis neurona.
In humans, nitazoxanide is approved (in the USA) for use in treating diarrhea caused by Cryptosporidium parvum and Giardia lamblia in pediatric patients from ages 1 to 11 years old.
Because of the drug’s spectrum of activity and apparent safety, there is considerable interest in using it in a variety of companion animal species, but data is lacking for specific indications and dosages.
Metabolism Nitazoxanide is available as powder that is reconstituted and dispensed as an oral suspension. The drug is well absorbed from the GI tract and rapidly metabolized, with elimination products appearing in the urine and feces. The only identified products in the plasma are TIZ and its glucuronide. The product can be taken with food.
storage Store at -20°C
References References/Citations:
1.Qu et al. (2018), Small molecule promotes b-catenin citrullination and inhibits Wnt signaling in cancer; Nat.Chem.Biol. 14 94
2.White (2004) Nitazoxanide: a new broad spectrum antiparasitic agent; Expert Rev.Anti.Infect.Ther. 2 43
3.Rossignol (2014) Nitazoxanide: a first-in-class broad-spectrum antiviral agent; Antiviral Res. 110 94
4.Hoffman et al. (2007) Antiparasitic Drug Nitazoxanide Inhibits the Pyruvate Oxidoreductases of Helicobacter pylori, Selected anaerobic Bacteria and Parasites, and Campylobacter jejuni; Agents Chemother. 51 868 5.Elazar et al. (2009), The anti-hepatitis C agent nitazoxanide induces phosphorylation of eukaryotic initiation factor 2alpha via protein kinase activated by double-stranded RNA activation; Gastroenterology 137 1827