Tiabendazole

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Tiabendazole
Thiabendazole.svg
Thiabendazole ball-and-stick.png
Clinical data
Trade names Mintezol, others
AHFS/Drugs.com International Drug Names
Pregnancy
category
    Routes of
    administration
    By mouth, topical
    ATC code
    Legal status
    Legal status
    • AU: S4 (Prescription only)
    • In general: ℞ (Prescription only)
    Pharmacokinetic data
    Bioavailability Сmax 1–2 hours (oral administration)
    Metabolism GI tract
    Elimination half-life 8 hours
    Excretion Urine (90%)
    Identifiers
    CAS Number
    PubChem CID
    IUPHAR/BPS
    DrugBank
    ChemSpider
    UNII
    KEGG
    ChEMBL
    NIAID ChemDB
    CompTox Dashboard (EPA)
    ECHA InfoCard 100.005.206 OOjs UI icon edit-ltr-progressive.svg
    Chemical and physical data
    Formula C10H7N3S
    Molar mass 201.25 g·mol−1
    3D model (JSmol)
    Density 1.103 g/cm3
    Melting point 293 to 305 °C (559 to 581 °F)
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    Tiabendazole (INN, BAN), also known as thiabendazole (AAN, USAN) or TBZ and the trade names Mintezol, Tresaderm, and Arbotect, is a preservative, [1] an antifungal agent, and an antiparasitic agent.

    Contents

    Uses

    Preservative

    Tiabendazole is used primarily to control mold, blight, and other fungal diseases in fruits (e.g. oranges) and vegetables; it is also used as a prophylactic treatment for Dutch elm disease.

    Tiabendazole is also used as a food additive, [2] [3] a preservative with E number E233 (INS number 233). For example, it is applied to bananas to ensure freshness, and is a common ingredient in the waxes applied to the skins of citrus fruits. It is not approved as a food additive in the EU, [4] Australia and New Zealand. [5]

    Use in treatment of aspergillosis has been reported. [6]

    It is also used in anti-fungal wallboards as a mixture with azoxystrobin.

    Parasiticide

    As an antiparasitic, tiabendazole is able to control roundworms (such as those causing strongyloidiasis), [7] hookworms, and other helminth species which infect wild animals, livestock, and humans. [8]

    Other

    In dogs and cats, tiabendazole is used to treat ear infections.[ clarification needed ]

    Tiabendazole is also a chelating agent, which means it is used medicinally to bind metals in cases of metal poisoning, such as lead, mercury, or antimony poisoning.[ medical citation needed ]

    Research

    Genes responsible for the maintenance of cell walls in yeast have been shown to be responsible for angiogenesis in vertebrates. Tiabendazole serves to block angiogenesis in both frog embryos and human cells. It has also been shown to serve as a vascular disrupting agent to reduce newly established blood vessels. Tiabendazole has been shown to effectively do this in certain cancer cells. [9]

    Pharmacodynamics

    Tiabendazole works by inhibition of the mitochondrial, helminth-specific enzyme, fumarate reductase, with possible interaction with endogenous quinone. [10]

    Safety

    The substance appears to have a slight toxicity in higher doses, with effects such as liver and intestinal disorders at high exposure in test animals (just below LD50 level).[ citation needed ] Some reproductive disorders and decreasing weaning weight have been observed, also at high exposure. Effects on humans from use as a drug include nausea, vomiting, loss of appetite, diarrhea, dizziness, drowsiness, or headache; very rarely also ringing in the ears, vision changes, stomach pain, yellowing eyes and skin, dark urine, fever, fatigue, increased thirst and change in the amount of urine occur.[ citation needed ] Carcinogenic effects have been shown at higher doses. [11]

    Synthesis

    Intermediate arylamidine 2 is prepared by aluminium trichloride-catalyzed addition of aniline to the nitrile of 4-cyanothiazole (1). [12] [13] The amidine (2) is then converted to its N-chloro derivative 3 with sodium hypochlorite (NaOCl). Upon treatment with base, this undergoes a nitrene insertion reaction (4) to produce tiabendazole (5).

    Tiabendazole synthesis Thiabendazole synthesis.svg
    Tiabendazole synthesis

    An alternative synthesis involves reacting 4-thiazolecarboxamide with o-phenylenediamine in polyphosphoric acid. [14]

    Derivatives

    A number of derivatives of tiabendazole are also pharmaceutical drugs, including albendazole, cambendazole, fenbendazole, oxfendazole, mebendazole, and flubendazole.

    Preparation of cambendazole Cambendazole synthesis.svg
    Preparation of cambendazole

    See also

    Related Research Articles

    Food additive substances added to food to preserve flavor or enhance its taste, appearance, or other qualities

    Food additives are substances added to food to preserve flavor or enhance its taste, appearance, or other qualities. Some additives have been used for centuries; for example, preserving food by pickling, salting, as with bacon, preserving sweets or using sulfur dioxide as with wines. With the advent of processed foods in the second half of the twentieth century, many more additives have been introduced, of both natural and artificial origin. Food additives also include substances that may be introduced to food indirectly in the manufacturing process, through packaging, or during storage or transport.

    <i>Strongyloides stercoralis</i> Species of worm

    Strongyloides stercoralis is a human pathogenic parasitic roundworm causing the disease strongyloidiasis. Its common name in the US is threadworm. In the UK and Australia, however, the term threadworm can also refer to nematodes of the genus Enterobius, otherwise known as pinworms.

    Butylated hydroxytoluene antioxidant and food additive

    Butylated hydroxytoluene (BHT), also known as dibutylhydroxytoluene, is a lipophilic organic compound, chemically a derivative of phenol, that is useful for its antioxidant properties. BHT is widely used to prevent free radical-mediated oxidation in fluids and other materials, and the regulations overseen by the U.S. F.D.A.—which considers BHT to be "generally recognized as safe"—allow small amounts to be added to foods. Despite this, and the earlier determination by the National Cancer Institute that BHT was noncarcinogenic in an animal model, societal concerns over its broad use have been expressed. BHT has also been postulated as an antiviral drug, but as of March 2020, use of BHT as a drug is not supported by the scientific literature and it has not been approved by any drug regulatory agency for use as an antiviral.

    Ascariasis A disease caused by the parasitic roundworm Ascaris lumbricoides

    Ascariasis is a disease caused by the parasitic roundworm Ascaris lumbricoides. Infections have no symptoms in more than 85% of cases, especially if the number of worms is small. Symptoms increase with the number of worms present and may include shortness of breath and fever in the beginning of the disease. These may be followed by symptoms of abdominal swelling, abdominal pain, and diarrhea. Children are most commonly affected, and in this age group the infection may also cause poor weight gain, malnutrition, and learning problems.

    Antifungal Pharmaceutical fungicide or fungistatic used to treat and prevent mycosis

    An antifungal medication, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis (thrush), serious systemic infections such as cryptococcal meningitis, and others. Such drugs are usually obtained by a doctor's prescription, but a few are available OTC (over-the-counter).

    Helminthiasis Macroparasitic disease in which a part of the body is infected with parasitic worms

    Helminthiasis, also known as worm infection, is any macroparasitic disease of humans and other animals in which a part of the body is infected with parasitic worms, known as helminths. There are numerous species of these parasites, which are broadly classified into tapeworms, flukes, and roundworms. They often live in the gastrointestinal tract of their hosts, but they may also burrow into other organs, where they induce physiological damage.

    Albendazole chemical compound

    Albendazole, also known as albendazolum, is a medication used for the treatment of a variety of parasitic worm infestations. It is useful for giardiasis, trichuriasis, filariasis, neurocysticercosis, hydatid disease, pinworm disease, and ascariasis, among others. It is taken by mouth.

    Benzimidazole chemical compound

    Benzimidazole is a heterocyclic aromatic organic compound. This bicyclic compound consists of the fusion of benzene and imidazole. It is a colorless solid.

    Strongyloidiasis Human helminthiasis

    Strongyloidiasis is a human parasitic disease caused by the nematode called Strongyloides stercoralis, or sometimes S. fülleborni which is a type of helminth. It belongs to a group of nematodes called roundworms. This intestinal worm can cause a number of symptoms in people, principally skin symptoms, abdominal pain, diarrhea and weight loss, among many other specific and vague symptoms in disseminated disease, and severe life-threatening conditions through hyperinfection. In some people, particularly those who require corticosteroids or other immunosuppressive medication, Strongyloides can cause a hyperinfection syndrome that can lead to death if untreated. The diagnosis is made by blood and stool tests. The medication ivermectin is widely used to treat strongyloidiasis.

    Fumagillin chemical compound

    Fumagillin is a complex biomolecule and used as an antimicrobial agent. It was isolated in 1949 from the microbial organism Aspergillus fumigatus.

    Avermectin

    The avermectins are a series of drugs and pesticides used to treat parasitic worms and insect pests. They are a 16-membered macrocyclic lactone derivatives with potent anthelmintic and insecticidal properties. These naturally occurring compounds are generated as fermentation products by Streptomyces avermitilis, a soil actinomycete. Eight different avermectins were isolated in four pairs of homologue compounds, with a major (a-component) and minor (b-component) component usually in ratios of 80:20 to 90:10. Other anthelmintics derived from the avermectins include ivermectin, selamectin, doramectin, eprinomectin, moxidectin, and abamectin.

    Antiparasitics are a class of medications which are indicated for the treatment of parasitic diseases, such as those caused by helminths, amoeba, ectoparasites, parasitic fungi, and protozoa, among others. Antiparasitics target the parasitic agents of the infections by destroying them or inhibiting their growth; they are usually effective against a limited number of parasites within a particular class. Antiparasitics are one of the antimicrobial drugs which include antibiotics that target bacteria, and antifungals that target fungi. They may be administered orally, intravenously or topically.

    Nitazoxanide chemical compound

    Nitazoxanide is a broad-spectrum antiparasitic and broad-spectrum antiviral drug that is used in medicine for the treatment of various helminthic, protozoal, and viral infections. It is indicated for the treatment of infection by Cryptosporidium parvum and Giardia lamblia in immunocompetent individuals and has been repurposed for the treatment of influenza. Nitazoxanide has also been shown to have in vitro antiparasitic activity and clinical treatment efficacy for infections caused by other protozoa and helminths; emerging evidence suggests that it possesses efficacy in treating a number of viral infections as well.

    Pyruvate synthase class of enzymes

    In enzymology, a pyruvate synthase is an enzyme that catalyzes the interconversion of pyruvate and acetyl-CoA. It is also called pyruvate:ferredoxin oxidoreductase (PFOR).

    Amoscanate chemical compound

    Amoscanate (INN), also known as nithiocyamine, is an experimental anthelmintic agent of the arylisothiocyanate class which was found to be highly effective in animals against the four major species of schistosomes which infect humans, and is also highly active against hookworm infection. However, significant liver toxicity was seen in lab animals at higher doses. The ether analogue of amoscanate, nitroscanate, is used in veterinary medicine as an anthelmintic.

    Anthelmintic Antiparasitic drugs that expel parasitic worms (helminths) from the body

    Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. They may also be called vermifuges or vermicides. Anthelmintics are used to treat people who are infected by helminths, a condition called helminthiasis. These drugs are also used to treat infected animals.

    <i>Cooperia oncophora</i> species of Secernentea

    Cooperia oncophora is one of the most common intestinal parasitic nematodes in cattle in temperate regions. Infections with C. oncophora may result in mild clinical symptoms, but can lead to weight loss and damage of the small intestine, especially when co-infections with other nematodes such as O. ostertagi occur. Infections are usually treated with broad-spectrum anthelmintics such as benzimidazole, but resistance to these drugs has developed in the last decades and is now very common. C. oncophora has a direct life cycle. Infective larvae are ingested by the host. The larvae grow to adults, which reproduce in the small intestines. Eggs are shed onto the pasture with the faeces, which leads to new infections. Co-infections with other gastro-intestinal nematodes such as O. ostertagi and H. contortus are common.

    The fecal egg count reduction test was suggested in the World Association for the Advancement of Veterinary Parasitology guideline for estimating the reduction in fecal egg counts and its corresponding confidence interval. The results of this test can be used to determine the anthelmintic resistance status of the animals.

    References

    1. "E233 : E Number : Preservative". www.ivyroses.com. Retrieved 2018-08-28.
    2. Rosenblum, C (March 1977). "Non-Drug-Related Residues in Tracer Studies". Journal of Toxicology and Environmental Health. 2 (4): 803–14. doi:10.1080/15287397709529480. PMID   853540.
    3. Sax, N.I. Dangerous Properties of Industrial Materials. Vol 1-3 7th ed. New York, NY: Van Nostrand Reinhold, 1989., p. 3251
    4. UK Food Standards Agency: "Current EU approved additives and their E Numbers" . Retrieved 2011-10-27.
    5. Australia New Zealand Food Standards Code "Standard 1.2.4 – Labelling of ingredients" . Retrieved 2011-10-27.
    6. Upadhyay MP, West EP, Sharma AP (January 1980). "Keratitis due to Aspergillus flavus successfully treated with thiabendazole". Br J Ophthalmol. 64 (1): 30–2. doi:10.1136/bjo.64.1.30. PMC   1039343 . PMID   6766732.
    7. Igual-Adell R, Oltra-Alcaraz C, Soler-Company E, Sánchez-Sánchez P, Matogo-Oyana J, Rodríguez-Calabuig D (December 2004). "Efficacy and safety of ivermectin and thiabendazole in the treatment of strongyloidiasis". Expert Opin Pharmacother. 5 (12): 2615–9. doi:10.1517/14656566.5.12.2615. PMID   15571478. Archived from the original on 2016-03-06.
    8. Portugal R, Schaffel R, Almeida L, Spector N, Nucci M (June 2002). "Thiabendazole for the prophylaxis of strongyloidiasis in immunosuppressed patients with hematological diseases: a randomized double-blind placebo-controlled study". Haematologica. 87 (6): 663–4. PMID   12031927.
    9. Cha, HJ; Byrom M; Mead PE; Ellington AD; Wallingford JB; et al. (August 2012). "Evolutionarily Repurposed Networks Reveal the Well-Known Antifungal Drug Thiabendazole to Be a Novel Vascular Disrupting Agent". PLoS Biology. 10 (8): e1001379. doi:10.1371/journal.pbio.1001379. PMC   3423972 . PMID   22927795 . Retrieved 2012-08-21.
    10. Gilman, A.G.; T.W. Rall; A.S. Nies; P. Taylor, eds. (1990). Goodman and Gilman's The Pharmacological Basis of Therapeutics (8th ed.). New York, NY: Pergamon Press. p. 970.
    11. "Reregistration Eligibility Decision Thiabendazole" (PDF). Environmental Protection Agency. Retrieved 8 January 2013.
    12. Setzinger, Meyer; Painfield, North; Gaines, Water A.; Grenda, Victor J. (1965). "Novel Preparation of Benzimidazoles from N-Arylamidines. New Synthesis of Thiabendazole1". The Journal of Organic Chemistry. 30: 259–261. doi:10.1021/jo01012a061.
    13. L. H. Sarett, H. D. Brown, U.S. Patent 3,299,081 (1967 to Merck & Co.)
    14. Brown, H. D.; Matzuk, A. R.; Ilves, I. R.; Peterson, L. H.; Harris, S. A.; Sarett, L. H.; Egerton, J. R.; Yakstis, J. J.; Campbell, W. C.; Cuckler, A. C. (1961). "Antiparasitic Drugs. Iv. 2-(4'-Thiazolyl)-Benzimidazole, A New Anthelmintic". Journal of the American Chemical Society. 83 (7): 1764–1765. doi:10.1021/ja01468a052.
    15. Hoff, Fisher, ZA 6800351 (1969 to Merck & Co.), C.A. 72, 90461q (1970).
    16. Hoff, D. R.; Fisher, M. H.; Bochis, R. J.; Lusi, A.; Waksmunski, F.; Egerton, J. R.; Yakstis, J. J.; Cuckler, A. C.; Campbell, W. C. (1970). "A new broad-spectrum anthelmintic: 2-(4-Thiazolyl)-5-isopropoxycarbonylamino-benzimidazole". Experientia. 26 (5): 550–551. doi:10.1007/BF01898506.