55981-09-4 Usage
Uses
1. Used in Antiviral Applications:
Nitazoxanide is used as an antiviral agent for testing its activity against chikungunya virus.
2. Used in Antiprotozoal Applications:
Nitazoxanide is used as an antiprotozoal agent for treating giardiasis and cryptosporidiosis, particularly in children and immunosuppressed patients.
3. Used in Cancer Research:
Nitazoxanide is used as a test compound for evaluating its effect on cell viability in various cancer cell lines.
4. Used in Infectious Disease Research:
Nitazoxanide is used as a test compound for examining its effect on human cytomegalovirus (HCMV) infected human fibroblast HFF cells.
5. Used in Helminth Infections:
Nitazoxanide is used as an anthelmintic for treating cestode infections.
6. Used in Tuberculosis Treatment:
Nitazoxanide is used as an antimicrobial agent for killing Mycobacterium tuberculosis.
7. Used in Hypertension Management:
Nitazoxanide is used as an antihypertensive agent for managing high blood pressure.
8. Used in Pharmaceutical Industry:
Nitazoxanide is used as an active pharmaceutical ingredient in the development of drugs for various applications, such as treating diarrhea caused by Giardia lamblia and Cryptosporidium parvum.
Originator
Alinia,Romark Laboratories, L.C.
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.
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.
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 Cmax
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.
References
References/Citations:
Check Digit Verification of cas no
The CAS Registry Mumber 55981-09-4 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 5,5,9,8 and 1 respectively; the second part has 2 digits, 0 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 55981-09:
(7*5)+(6*5)+(5*9)+(4*8)+(3*1)+(2*0)+(1*9)=154
154 % 10 = 4
So 55981-09-4 is a valid CAS Registry Number.
InChI:InChI=1/C12H9N3O5S/c1-7(16)20-9-5-3-2-4-8(9)11(17)14-12-13-6-10(21-12)15(18)19/h2-6H,1H3,(H,13,14,17)
55981-09-4Relevant articles and documents
Synthesis and antiplasmodial assessment of nitazoxanide and analogs as new antimalarial candidates
Aguiar, Anna Caroline Campos,Guido, Rafael Victorio Carvalho,Irabuena, Camila,Mendes, Giovana Rossi,Scarone, Laura,Serra, Gloria,de Souza, Guilherme Eduardo
, (2022/02/07)
During the last years, the progression to control malaria disease seems to be slowed and WHO (World Health Organization) reported a modeling analysis with the prediction of the increase in malaria morbidity and mortality in sub-Saharan Africa during the COVID-19 pandemic. A rapid way to the discovery of new drugs could be carried out by performing investigations to identify drugs based on repurposing of “old” drugs. The 5-nitrothiazole drug, Nitazoxanide was shown to be active against intestinal protozoa, human helminths, anaerobic bacteria, viruses, etc. In this work, Nitazoxanide and analogs were prepared using two methodologies and evaluated against P. falciparum 3D7. A bithiazole analog, showed attractive inhibitory activity with an EC50 value of 5.9 μM, low propensity to show toxic effect against HepG2 cells at 25 μM, and no cross-resistance with standard antimalarials.
Thiazole compound as well as preparation method and application thereof
-
Paragraph 0117-0119; 0121-0123, (2021/08/21)
The invention relates to thiazole compounds as well as a preparation method and application thereof, and belongs to the field of medicinal chemistry. The compound has a structural general formula described in the specifications of the invention; the compound or the prodrug thereof or pharmaceutically acceptable salts of the compound not only can significantly improve the biological activity, but also can effectively reduce the loss of biological activity due to glycosylation, significantly improve the exposure of effective drugs, and can be used for preparing medicines for preventing or treating hepatic fibrosis, medicines for preventing or treating viral influenza, medicines for treating Alzheimer's disease and Parkinson's disease and the like, and the clinical application of the compound is expanded.
Silver(I)-Promoted ipso-Nitration of Carboxylic Acids by Nitronium Tetrafluoroborate
Natarajan, Palani,Chaudhary, Renu,Venugopalan, Paloth
, p. 10498 - 10504 (2015/11/18)
A novel and efficient method for the regioselective nitration of a series of aliphatic and aromatic carboxylic acids to their corresponding nitro compounds using nitronium tetrafluoroborate and silver carbonate in dimethylacetamide has been described. This transformation is believed to proceed via the alkyl-silver or aryl-silver intermediate, which subsequently reacts with the nitronium ion to form nitro substances. Mild reaction conditions, tolerant of a broad range of functional groups, and formation of only the ipso-nitrated products are the key features of this methodology when compared to known methods for syntheses of nitroalkyls and nitroarenes.
