Trade names Mintezol, others Routes of
administration By mouth, topical Molar mass 201.249 g/mol Density 1.103 g/cm³ | Pregnancy
category AU: B3 Formula C10H7N3S CAS ID 148-79-8 | |
 | ||
AHFS/Drugs.com International Drug Names ATC code D01AC06 (WHO) P02CA02 (WHO) QP52AC10 (WHO) Legal status AU: S4 (Prescription only)
In general: ℞ (Prescription only) | ||
Tiabendazole (INN, BAN), thiabendazole (AAN, USAN), TBZ (and the trade names Mintezol, Tresaderm, and Arbotect) is a fungicide and parasiticide.
Contents
Fungicide
It 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.
Use in treatment of aspergillosis has been reported.
Parasiticide
As an antiparasitic, it is able to control roundworms (such as those causing strongyloidiasis), hookworms, and other helminth species which attack wild animals, livestock and humans.
Angiogenesis inhibitor
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
TBZ works by inhibition of the mitochondrial, helminth-specific enzyme, fumarate reductase, with possible interaction with endogenous quinone.
Other
Medicinally, thiabendazole 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.
In dogs and cats, thiabendazole is used to treat ear infections.
Thiabendazole is also used as a food additive, 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, Australia and New Zealand.
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). 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 arylamidine 2 is prepared by the AlCl3 catalyzed addition of aniline to the nitrile function of 4-cyanothiazole (1). Amidine (2) is then converted to its N-chloro analog 3 by means of NaOCl. On base treatment, this apparently undergoes a nitrene insertion reaction (4) to produce thiabendazole (5). Note the direction of the arrow is from the benzene to the nitrene since the nitrene is an electrophilic species.
Alternative route of synthesis: 4-thiazolecarboxamide with o-phenylenediamine in polyphosphoric acid.
Synthesis of labeled thiabendazole:
Analogues
Cambendazole (best of 300 agents in an extensive study), is made by nitration of tiabendazole, followed by catalytic hydrogenation to 2, and acylation with Isopropyl chloroformate.
Additionally, tiabendazole was noted to exhibit moderate anti-inflammatory and analgesic activities, which led to the development of KB-1043.