Tiabendazole

Last updated
Tiabendazole
Thiabendazole.svg
Thiabendazole ball-and-stick.png
Clinical data
Trade names Mintezol, others
AHFS/Drugs.com International Drug Names
Pregnancy
category
  • AU:B3
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

<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.

Sodium benzoate Chemical compound

Sodium benzoate is a substance which has the chemical formula C6H5COONa. It is a widely used food pickling agent, with an E number of E211. It is the sodium salt of benzoic acid and exists in this form when dissolved in water. It can be produced by reacting sodium hydroxide with benzoic acid.

An antimicrobial is an agent that kills microorganisms or stops their growth. Antimicrobial medicines can be grouped according to the microorganisms they act primarily against. For example, antibiotics are used against bacteria, and antifungals are used against fungi. They can also be classified according to their function. Agents that kill microbes are microbicides, while those that merely inhibit their growth are called bacteriostatic agents. The use of antimicrobial medicines to treat infection is known as antimicrobial chemotherapy, while the use of antimicrobial medicines to prevent infection is known as antimicrobial prophylaxis.

Imidazole Chemical compound

Imidazole is an organic compound with the formula C3N2H4. It is a white or colourless solid that is soluble in water, producing a mildly alkaline solution. In chemistry, it is an aromatic heterocycle, classified as a diazole, and has non-adjacent nitrogen atoms.

Ivermectin Medication for parasite infestations

Ivermectin is a medication used to treat many types of parasite infestations. In humans, this includes head lice, scabies, river blindness (onchocerciasis), strongyloidiasis, trichuriasis, ascariasis, and lymphatic filariasis. In veterinary medicine, it is used to prevent and treat heartworm and acariasis, among other indications. It can be taken by mouth or applied to the skin for external infestations.

Albendazole

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 other diseases It is taken orally.

Benzimidazole

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

Strongyloidiasis

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

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

Mebendazole Medication for parasitic worm infestations

Mebendazole (MBZ) is a medication used to treat a number of parasitic worm infestations. This includes ascariasis, pinworm disease, hookworm infections, guinea worm infections, hydatid disease, and giardia, among others. It is taken by mouth.

Benzoxazole

Benzoxazole is an aromatic organic compound with a molecular formula C7H5NO, a benzene-fused oxazole ring structure, and an odor similar to pyridine. Although benzoxazole itself is of little practical value, many derivatives of benzoxazoles are commercially important.

Beauvericin

Beauvericin is a depsipeptide with antibiotic and insecticidal effects belonging to the enniatin family. It was isolated from the fungus Beauveria bassiana, but is also produced by several other fungi, including several Fusarium species; it may therefore occur in grain contaminated with these fungi. Beauvericin is active against Gram-positive bacteria and mycobacteria, and is also capable of inducing programmed cell death in mammals.

Avermectin

The avermectins are a series of drugs and pesticides used to treat parasitic worms and insect pests. They are a group of 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, 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

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; evidence as of 2014 suggested that it possesses efficacy in treating a number of viral infections as well.

Bifonazole

Bifonazole is an imidazole antifungal drug used in form of ointments.

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>

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.

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.