Tiabendazole (

INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway; before the advent of motorized transportation they also provided accommo ...

, BAN), also known as thiabendazole ( AAN,

USAN 280px, "Samguk Sagi" Book 04. Silla's Records. In 512, Usan-guk（于山國）was Ulleungdo（鬱陵島） Usan-guk, or the State of Usan, occupied Ulleung-do and the adjacent islands during the Korean Three Kingdoms period. According to th ...

) or TBZ and the trade names Mintezol, Tresaderm, and Arbotect, is a preservative, an antifungal agent, and an antiparasitic agent.

Uses

Preservative

Tiabendazole is used primarily to control

mold A mold () or mould () is one of the structures certain fungi can form. The dust-like, colored appearance of molds is due to the formation of spores containing fungal secondary metabolites. The spores are the dispersal units of the fungi. Not ...

blight Blight refers to a specific symptom affecting plants in response to infection by a pathogenic organism. Description Blight is a rapid and complete chlorosis, browning, then death of plant tissues such as leaves, branches, twigs, or floral org ...

, and other fungal diseases in fruits (e.g.

oranges An orange is a fruit of various citrus species in the family Rutaceae (see list of plants known as orange); it primarily refers to ''Citrus'' × ''sinensis'', which is also called sweet orange, to distinguish it from the related ''Citrus × ...

) and vegetables; it is also used as a

prophylactic Preventive healthcare, or prophylaxis, consists of measures taken for the purposes of disease prevention.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental hea ...

treatment for

Dutch elm disease Dutch elm disease (DED) is caused by a member of the sac fungi (Ascomycota) affecting elm trees, and is spread by elm bark beetles. Although believed to be originally native to Asia, the disease was accidentally introduced into Americas, America ...

. Tiabendazole is also used as a food additive, a

preservative A preservative is a substance or a chemical that is added to products such as food products, beverages, pharmaceutical drugs, paints, biological samples, cosmetics, wood, and many other products to prevent decomposition by microbial growth or by ...

with E number E233 (

INS number The International Numbering System for Food Additives (INS) is a European-based naming system for food additives, aimed at providing a short designation of what may be a lengthy actual name."Class Names and the International Numbering System for Fo ...

233). For example, it is applied to

bananas A banana is an elongated, edible fruit – botanically a berry – produced by several kinds of large herbaceous flowering plants in the genus ''Musa''. In some countries, bananas used for cooking may be called "plantains", distinguis ...

to ensure freshness, and is a common ingredient in the

wax Waxes are a diverse class of organic compounds that are lipophilic, malleable solids near ambient temperatures. They include higher alkanes and lipids, typically with melting points above about 40 °C (104 °F), melting to giv ...

es applied to the skins of

citrus fruit ''Citrus'' is a genus of flowering trees and shrubs in the rue family, Rutaceae. Plants in the genus produce citrus fruits, including important crops such as oranges, lemons, grapefruits, pomelos, and limes. The genus ''Citrus'' is native to ...

s. It is not approved as a food additive in the EU, Australia and New Zealand. Use in treatment of

aspergillosis Aspergillosis is a fungal infection of usually the lungs, caused by the genus ''Aspergillus'', a common mould that is breathed in frequently from the air around, but does not usually affect most people. It generally occurs in people with lung di ...

has been reported. It is also used in anti-fungal

wallboard Drywall (also called plasterboard, dry lining, wallboard, sheet rock, gypsum board, buster board, custard board, and gypsum panel) is a panel made of calcium sulfate dihydrate (gypsum), with or without additives, typically extruded between thic ...

s as a mixture with

azoxystrobin Azoxystrobin is the ISO common name for an organic compound that is used as a fungicide. It is a broad spectrum systemic active ingredient widely used in agriculture to protect crops from fungal diseases. It was first marketed in 1996 using the ...

Parasiticide

As an antiparasitic, tiabendazole is able to control

roundworm The nematodes ( or grc-gre, Νηματώδη; la, Nematoda) or roundworms constitute the phylum Nematoda (also called Nemathelminthes), with plant-parasitic nematodes also known as eelworms. They are a diverse animal phylum inhabiting a bro ...

s (such as those causing

strongyloidiasis 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 wo ...

), hookworms, and other helminth species which infect wild animals,

livestock Livestock are the domesticated animals raised in an agricultural setting to provide labor and produce diversified products for consumption such as meat, eggs, milk, fur, leather, and wool. The term is sometimes used to refer solely to animal ...

, and humans.

Other

In dogs and cats, tiabendazole is used to treat ear infections. Tiabendazole is also a

chelating agent Chelation is a type of bonding of ions and molecules to metal ions. It involves the formation or presence of two or more separate coordinate bonds between a polydentate (multiple bonded) ligand and a single central metal atom. These ligands ar ...

, which means it is used medicinally to bind metals in cases of metal poisoning, such as

lead Lead is a chemical element with the symbol Pb (from the Latin ) and atomic number 82. It is a heavy metal that is denser than most common materials. Lead is soft and malleable, and also has a relatively low melting point. When freshly cu ...

, mercury, or

antimony Antimony is a chemical element with the symbol Sb (from la, stibium) and atomic number 51. A lustrous gray metalloid, it is found in nature mainly as the sulfide mineral stibnite (Sb2S3). Antimony compounds have been known since ancient t ...

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.

Pharmacodynamics

Tiabendazole works by inhibition of the mitochondrial, helminth-specific enzyme,

fumarate reductase Fumarate reductase is the enzyme that converts fumarate to succinate, and is important in microbial metabolism as a part of anaerobic respiration. Succinate + acceptor fumarate + reduced acceptor Fumarate reductases can be divided into two classe ...

, with possible interaction with endogenous quinone.

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 level). 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. Carcinogenic effects have been shown at higher doses.

Synthesis

Intermediate aryl

amidine Amidines are organic compounds with the functional group RC(NR)NR2, where the R groups can be the same or different. They are the imine derivatives of amides (RC(O)NR2). The simplest amidine is formamidine, HC(=NH)NH2. Examples of amidines includ ...

2 is prepared by

aluminium trichloride Aluminium chloride, also known as aluminium trichloride, is an inorganic compound with the formula . It forms hexahydrate with the formula , containing six water molecules of hydration. Both are colourless crystals, but samples are often conta ...

-catalyzed addition of

aniline Aniline is an organic compound with the formula C6 H5 NH2. Consisting of a phenyl group attached to an amino group, aniline is the simplest aromatic amine. It is an industrially significant commodity chemical, as well as a versatile starti ...

to the nitrile of 4-cyanothiazole (1). The amidine (2) is then converted to its ''N''-chloro derivative 3 with

sodium hypochlorite Sodium hypochlorite (commonly known in a dilute solution as bleach) is an inorganic chemical compound with the formula NaOCl (or NaClO), comprising a sodium cation () and a hypochlorite anion (or ). It may also be viewed as the sodium s ...

(NaOCl). Upon treatment with base, this undergoes a

nitrene In chemistry, a nitrene or imene () is the nitrogen analogue of a carbene. The nitrogen atom is uncharged and univalent, so it has only 6 electrons in its valence level—two covalent bonded and four non-bonded electrons. It is therefore consid ...

insertion reaction (4) to produce tiabendazole (5). Thiabendazole synthesis

An alternative synthesis involves reacting 4-thiazolecarboxamide with ''o''-phenylenediamine in polyphosphoric acid.

Derivatives

A number of derivatives of tiabendazole are also pharmaceutical drugs, including

albendazole Albendazole (also known as albendazolum) is a broad-spectrum anthelmintic and antiprotozoal agent of the benzimidazole type. It is used for the treatment of a variety of intestinal parasite infections, including ascariasis, pinworm infection, ho ...

, cambendazole,

fenbendazole Fenbendazole is a broad spectrum benzimidazole anthelmintic used against gastrointestinal parasites including: giardia, roundworms, hookworms, whipworms, the tapeworm genus '' Taenia'' (but not effective against '' Dipylidium caninum'', a comm ...

oxfendazole 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. Oxfendazole is an anthelmintic (wormer ...

mebendazole 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 disea ...

, and

flubendazole Flubendazole is an anthelmintic. Its brand name is Flutelmium which is a paste manufactured by Janssen Pharmaceutica N.V. used by veterinarians for protection against internal parasites and worms in dogs and cats. Other brand names are Flubenol, ...

References

External links

Thiabendazole, Extension Toxicology Network

{{Authority control Antiparasitic agents Benzimidazoles Fungicides Preservatives Thiazoles