Tiabendazole
Tiabendazole
Chemical compound
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.
| Clinical data | |
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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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| ECHA InfoCard | 100.005.206  |
| 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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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] First approved for use in sheep in 1961 and horses in 1962, resistance to this drug was first found in Haemonchus contortus in 1964, and then in the two other major small ruminant nematode parasites, Teladorsagia circumcincta and Trichostrongylus colubriformis.[9]
Fungicide
Tiabendazole acts as a fungicide through binding fungal tubulin. Resistant Aspergillus nidulans specimens were found to have a mutation in the gene coding for β-tubulin, which was reversible by a mutation in the gene for α-tubulin. This showed that thiabendazole binds to both α- and β-tubulin.[10]
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]
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.[11]
Tiabendazole works by inhibition of the mitochondrial, helminth-specific enzyme, fumarate reductase, with possible interaction with endogenous quinone.[12]
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.[13]
Intermediate arylamidine 2 is prepared by aluminium trichloride-catalyzed addition of aniline to the nitrile of 4-cyanothiazole (1).[14][15] 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.[16]
Derivatives
A number of derivatives of tiabendazole are also pharmaceutical drugs, including albendazole, cambendazole, fenbendazole, oxfendazole, mebendazole, and flubendazole.
- "E233 : E Number : Preservative". www.ivyroses.com. Retrieved 2018-08-28.
- Rosenblum C (March 1977). "Non-drug-related residues in tracer studies". Journal of Toxicology and Environmental Health. 2 (4): 803–814. Bibcode:1977JTEH....2..803R. doi:10.1080/15287397709529480. PMID 853540.
- Sax NI (1989). Dangerous Properties of Industrial Materials. Vol. 1–3 (7th ed.). New York, NY: Van Nostrand Reinhold. p. 3251.
- UK Food Standards Agency: "Current EU approved additives and their E Numbers". Retrieved 2011-10-27.
- Australia New Zealand Food Standards Code"Standard 1.2.4 – Labelling of ingredients". 8 September 2011. Retrieved 2011-10-27.
- Upadhyay MP, West EP, Sharma AP (January 1980). "Keratitis due to Aspergillus flavus successfully treated with thiabendazole". The British Journal of Ophthalmology. 64 (1): 30–32. doi:10.1136/bjo.64.1.30. PMC 1039343. PMID 6766732.
- 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 Opinion on Pharmacotherapy. 5 (12): 2615–2619. doi:10.1517/14656566.5.12.2615. PMID 15571478. S2CID 23721306. Archived from the original on 2016-03-06.
- 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): 663–664. PMID 12031927.
- Kaplan, Ray M. (October 2004). "Drug resistance in nematodes of veterinary importance: a status report". Trends in Parasitology. 20 (10): 477–481. doi:10.1016/j.pt.2004.08.001. ISSN 1471-4922. PMID 15363441.
- Wang, C. C. (January 1984). "Parasite enzymes as potential targets for antiparasitic chemotherapy". Journal of Medicinal Chemistry. 27 (1): 1–9. doi:10.1021/jm00367a001. ISSN 0022-2623. PMID 6317859.
- Cha HJ, Byrom M, Mead PE, Ellington AD, Wallingford JB, Marcotte EM (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.
- Gilman AG, Rall TW, Nies AS, Taylor P, eds. (1990). Goodman and Gilman's The Pharmacological Basis of Therapeutics (8th ed.). New York, NY: Pergamon Press. p. 970.
- "Reregistration Eligibility Decision Thiabendazole" (PDF). Environmental Protection Agency. Retrieved 8 January 2013.
- Grenda VJ, Jones RE, Gal G, Sletzinger M (1965). "Novel Preparation of Benzimidazoles from N-Arylamidines. New Synthesis of Thiabendazole". The Journal of Organic Chemistry. 30: 259–261. doi:10.1021/jo01012a061.
- US 3336192, Sarett LH, Brown HD, "Anthelmintic substituted benzimidazole compositions", issued 1967, assigned to Merck & Co.
- Brown HD, Matzuk AR, Ilves I, Peterson LH, Harris SA, Sarett LH, et al. (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.
- ZA 6800351, Hoff DR, Fisher MH, "Anthelmintic 5-substituted aminobenzimidazoles", issued 1969, assigned to Merck and Co., Inc. Chemical Abstracts 72, 90461 (1970).