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
  • 4-(1H-1,3-Benzodiazol-2-yl)-1,3-thiazole
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)
  • [nH]1c2ccccc2nc1c3cscn3
  • InChI=1S/C10H7N3S/c1-2-4-8-7(3-1)12-10(13-8)9-5-14-6-11-9/h1-6H,(H,12,13) X mark.svgN
  • Key:WJCNZQLZVWNLKY-UHFFFAOYSA-N X mark.svgN
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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. [ 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]

This chemical is also used as a pesticide, including to treat Beech Leaf Disease. [11]

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. [12]

Pharmacodynamics

Tiabendazole works by inhibition of the mitochondrial, helminth-specific enzyme, fumarate reductase, with possible interaction with endogenous quinone. [13]

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. [14]

Synthesis

Intermediate aryl amidine (2) is prepared by aluminium trichloride-catalyzed addition of aniline to the nitrile of 4-cyanothiazole (1). [15] [16] 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. [17]

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

<span class="mw-page-title-main">Ascariasis</span> 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.

<span class="mw-page-title-main">Ivermectin</span> Medication for parasite infestations

Ivermectin is an antiparasitic drug. After its discovery in 1975, its first uses were in veterinary medicine to prevent and treat heartworm and acariasis. Approved for human use in 1987, it is used to treat infestations including head lice, scabies, river blindness (onchocerciasis), strongyloidiasis, trichuriasis, ascariasis and lymphatic filariasis. It works through many mechanisms to kill the targeted parasites, and can be taken by mouth, or applied to the skin for external infestations. It belongs to the avermectin family of medications.

<span class="mw-page-title-main">Albendazole</span> Chemical compound

Albendazole is a broad-spectrum antihelmintic and antiprotozoal agent of the benzimidazole type. It is used for the treatment of a variety of intestinal parasite infections, including ascariasis, pinworm infection, hookworm infection, trichuriasis, strongyloidiasis, taeniasis, clonorchiasis, opisthorchiasis, cutaneous larva migrans, giardiasis, and gnathostomiasis, among other diseases.

<span class="mw-page-title-main">Benzimidazole</span> Chemical compound

Benzimidazole is a heterocyclic aromatic organic compound. This bicyclic compound may be viewed as fused rings of the aromatic compounds benzene and imidazole. It is a white solid that appears in form of tabular crystals.

<span class="mw-page-title-main">Piperazine</span> Chemical compound

Piperazine is an organic compound that consists of a six-membered ring containing two nitrogen atoms at opposite positions in the ring. Piperazine exists as small alkaline deliquescent crystals with a saline taste.

<span class="mw-page-title-main">Strongyloidiasis</span> Medical condition

Strongyloidiasis is a human parasitic disease caused by the nematode called Strongyloides stercoralis, or sometimes the closely related S. fülleborni. These helminths belong to a group of nematodes called roundworms. These intestinal worms can cause a number of symptoms in people, principally skin symptoms, abdominal pain, diarrhea and weight loss, but also 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.

<span class="mw-page-title-main">Mebendazole</span> Medication for parasitic worm infestations

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

<span class="mw-page-title-main">2-Phenylphenol</span> Chemical compound

2-Phenylphenol, or o-phenylphenol, is an organic compound. In terms of structure, it is one of the monohydroxylated isomers of biphenyl. It is a white solid. It is a biocide used as a preservative with E number E231 and under the trade names Dowicide, Torsite, Fungal, Preventol, Nipacide and many others.

<span class="mw-page-title-main">Fenbendazole</span> Chemical compound

Fenbendazole is a broad spectrum benzimidazole anthelmintic used against gastrointestinal parasites including: giardia, roundworms, hookworms, whipworms, the tapeworm genus Taenia, pinworms, aelurostrongylus, paragonimiasis, strongyles, and strongyloides that can be administered to sheep, cattle, horses, fish, dogs, cats, rabbits, most reptiles, freshwater shrimp tanks as planaria and hydra treatments, as well as seals.

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. Overuse or misuse of antiparasitics can lead to the development of antimicrobial resistance.

<span class="mw-page-title-main">Benzimidazole fungicide</span> Class of chemical compounds

Benzimidazole fungicides are a class of fungicides including benomyl, carbendazim (MBC), thiophanate-methyl, thiabendazole and fuberidazole. They can control many ascomycetes and basidiomycetes, but not oomycetes. They are applied to cereals, fruits, vegetables and vines, and are also used in postharvest handling of crops.

<span class="mw-page-title-main">Nitazoxanide</span> Broad-spectrum antiparasitic and antiviral medication

Nitazoxanide, sold under the brand name Alinia among others, is a broad-spectrum antiparasitic and broad-spectrum antiviral medication 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.

<i>Helminthosporium solani</i> Species of fungus

Helminthosporium solani is a fungal plant pathogen responsible for the plant disease known as silver scurf. Silver scurf is a blemish disease, meaning the effect it has on tubers is mostly cosmetic and affects "fresh market, processing and seed tuber potatoes." There are some reports of it affecting development, meaning growth and tuber yield. This is caused by light brown lesions, which in turn change the permeability of tuber skin and then it causes tuber shrinkage and water loss, which finally causes weight loss. The disease has become economically important because silver scurf affected potatoes for processing and direct consumption have been rejected by the industry. The disease cycle can be divided into two stages: field and storage. It is mainly a seed borne disease and the primary source of inoculum is mainly infected potato seed tubers. Symptoms develop and worsen in storage because the conditions are conducive to sporulation. The ideal conditions for the spread of this disease are high temperatures and high humidity. There are also many cultural practices that favor spread and development. There are multiple ways to help control the disease.

<span class="mw-page-title-main">Pyruvate synthase</span> 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).

<span class="mw-page-title-main">Flubendazole</span> Chemical compound

Flubendazole is an anthelmintic, used both in humans and for veterinarian purposes. It is very close chemically to mebendazole, the only difference being an added fluorine group.

Ascaricides are drugs to treat ascariasis that is caused by infections with parasitic nematodes (roundworms) of the genus Ascaris. The large roundworm of pigs typically infects pigs while Ascaris lumbricoides affects human populations, typically in sub-tropical and tropical areas with poor sanitation. Ascaricides belong to the group of drugs collectively called anthelmintics which 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.

<span class="mw-page-title-main">Anthelmintic</span> 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, particularly small ruminants such as goats and sheep.

<span class="mw-page-title-main">Oxfendazole</span> Chemical compound

Oxfendazole is a broad spectrum benzimidazole anthelmintic. Its main use is for protecting livestock against roundworm, strongyles and pinworms. Oxfendazole is the sulfoxide metabolite of fenbendazole.

<i>Cooperia oncophora</i> Species of roundworm

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): 803–814. Bibcode:1977JTEH....2..803R. doi:10.1080/15287397709529480. PMID   853540.
  3. ↑ Sax NI (1989). Dangerous Properties of Industrial Materials. Vol. 1–3 (7th ed.). New York, NY: Van Nostrand Reinhold. 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". 8 September 2011. Retrieved 2011-10-27.
  6. ↑ 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.
  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 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.
  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): 663–664. PMID   12031927.
  9. ↑ 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.
  10. ↑ 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.
  11. ↑ "Beech Leaf Disease". UMass Extension Landscape, Nursery and Urban Forestry Program. University of Massachusetts Amherst. Retrieved 30 July 2024.
  12. ↑ 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.
  13. ↑ 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.
  14. ↑ "Reregistration Eligibility Decision Thiabendazole" (PDF). Environmental Protection Agency. Retrieved 8 January 2013.
  15. ↑ 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.
  16. ↑ US 3336192,Sarett LH, Brown HD,"Anthelmintic substituted benzimidazole compositions",issued 1967, assigned to Merck & Co.
  17. ↑ 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.
  18. ↑ ZA 6800351,Hoff DR, Fisher MH,"Anthelmintic 5-substituted aminobenzimidazoles",issued 1969, assigned to Merck and Co., Inc. Chemical Abstracts 72, 90461 (1970).
  19. ↑ Hoff DR, Fisher MH, Bochis RJ, Lusi A, Waksmunski F, Egerton JR, et al. (May 1970). "A new broad-spectrum anthelmintic: 2-(4-thiazolyl)-5-isopropoxycarbonylamino-benzimidazole". Experientia. 26 (5): 550–551. doi:10.1007/BF01898506. PMID   4245814. S2CID   26567527.
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