Chemistry:Tiabendazole
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| Trade names | Mintezol, others |
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| Routes of administration | By mouth, topical |
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| Pharmacokinetic data | |
| Bioavailability | Сmax 1–2 hours (oral administration) |
| Metabolism | GI tract |
| Elimination half-life | 8 hours |
| Excretion | Urine (90%) |
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| Chemical and physical data | |
| Formula | C10H7N3S |
| Molar mass | 201.25 g·mol−1 |
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| 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.
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. [citation needed]
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.[citation needed]
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.
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 -1">50 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).
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.
See also
- Fungicide use in the United States
- List of fungicides
References
- ↑ "E233 : E Number : Preservative" (in en-GB). http://www.ivyroses.com/Define/E233.
- ↑ "Non-drug-related residues in tracer studies". Journal of Toxicology and Environmental Health 2 (4): 803–814. March 1977. doi:10.1080/15287397709529480. PMID 853540.
- ↑ Dangerous Properties of Industrial Materials. 1–3 (7th ed.). New York, NY: Van Nostrand Reinhold. 1989. p. 3251.
- ↑ UK Food Standards Agency: "Current EU approved additives and their E Numbers". http://www.food.gov.uk/safereating/chemsafe/additivesbranch/enumberlist.
- ↑ Australia New Zealand Food Standards Code"Standard 1.2.4 – Labelling of ingredients". 8 September 2011. http://www.comlaw.gov.au/Details/F2011C00827.
- ↑ "Keratitis due to Aspergillus flavus successfully treated with thiabendazole". The British Journal of Ophthalmology 64 (1): 30–32. January 1980. doi:10.1136/bjo.64.1.30. PMID 6766732.
- ↑ "Efficacy and safety of ivermectin and thiabendazole in the treatment of strongyloidiasis". Expert Opinion on Pharmacotherapy 5 (12): 2615–2619. December 2004. doi:10.1517/14656566.5.12.2615. PMID 15571478. http://www.informapharmascience.com/doi/abs/10.1517/14656566.5.12.2615.
- ↑ "Thiabendazole for the prophylaxis of strongyloidiasis in immunosuppressed patients with hematological diseases: a randomized double-blind placebo-controlled study". Haematologica 87 (6): 663–664. June 2002. PMID 12031927. http://www.haematologica.org/cgi/pmidlookup?view=long&pmid=12031927.
- ↑ "Evolutionarily repurposed networks reveal the well-known antifungal drug thiabendazole to be a novel vascular disrupting agent". PLOS Biology 10 (8): e1001379. August 2012. doi:10.1371/journal.pbio.1001379. PMID 22927795.
- ↑ Goodman and Gilman's The Pharmacological Basis of Therapeutics (8th ed.). New York, NY: Pergamon Press. 1990. p. 970.
- ↑ "Reregistration Eligibility Decision Thiabendazole". Environmental Protection Agency. http://www.epa.gov/oppsrrd1/REDs/thiabendazole_red.pdf.
- ↑ "Novel Preparation of Benzimidazoles from N-Arylamidines. New Synthesis of Thiabendazole". The Journal of Organic Chemistry 30: 259–261. 1965. doi:10.1021/jo01012a061.
- ↑ Sarett LH, Brown HD, "Anthelmintic substituted benzimidazole compositions", US patent 3336192, issued 1967, assigned to Merck & Co.
- ↑ "Antiparasitic Drugs. IV. 2-(4'-Thiazolyl)-Benzimidazole, A New Anthelmintic". Journal of the American Chemical Society 83 (7): 1764–1765. 1961. doi:10.1021/ja01468a052.
- ↑ Hoff DR, Fisher MH, "Anthelmintic 5-substituted aminobenzimidazoles", ZA patent 6800351, issued 1969, assigned to Merck and Co., Inc. Chemical Abstracts 72, 90461 (1970).
- ↑ "A new broad-spectrum anthelmintic: 2-(4-thiazolyl)-5-isopropoxycarbonylamino-benzimidazole". Experientia 26 (5): 550–551. May 1970. doi:10.1007/BF01898506. PMID 4245814.
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