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Revision as of 08:40, 28 October 2011 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Script assisted update of identifiers for the Chem/Drugbox validation project (updated: 'DrugBank', 'ChEMBL').← Previous edit		Latest revision as of 19:26, 17 September 2024 edit undoHiya Moto (talk | contribs)4 edits →SynthesisTag: Visual edit
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			{{Short description|Chemical compound}}
	{{Drugbox		{{Drugbox
	| Verifiedfields = changed		| Verifiedfields = changed
			| Watchedfields = changed
	| verifiedrevid = 408934464
			| verifiedrevid = 457788234
	| IUPAC_name = 4-(1''H''-1,3-benzodiazol-2-yl)-1,3-thiazole
			| IUPAC_name = 4-(1''H''-1,3-Benzodiazol-2-yl)-1,3-thiazole
	| image = Thiabendazole structure.png
			| image = Thiabendazole.svg
	| width = 148
			| width = 150
			| image2 = Thiabendazole ball-and-stick.png
	<!--Clinical data-->		<!--Clinical data-->
	| tradename =		| tradename = Mintezol, others
	| Drugs.com = {{drugs.com|international|tiabendazole}}		| Drugs.com = {{drugs.com|international|tiabendazole}}
	| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->		| pregnancy_AU = B3
			| pregnancy_category =
	| pregnancy_US = <!-- A / B / C / D / X -->
			| legal_AU = S4
	| pregnancy_category =
	| legal_AU = <!-- Unscheduled / S2 / S4 / S8 -->
	| legal_UK = <!-- GSL / P / POM / CD -->		| legal_UK = <!-- GSL / P / POM / CD -->
	| legal_US = <!-- OTC / Rx-only -->		| legal_US = <!-- OTC / Rx-only -->
	| legal_status =		| legal_status = Rx-only
	| routes_of_administration =		| routes_of_administration = ], ]
	<!--Pharmacokinetic data-->		<!--Pharmacokinetic data-->
	| bioavailability =		| bioavailability = ] 1–2 hours (oral administration)
	| protein_bound =		| protein_bound =
	| metabolism = GI tract. Peak plasma 1-2 hours through oral admin.		| metabolism = GI tract
	| elimination_half-life = 8 hours		| elimination_half-life = 8 hours
	| excretion = 90% Urine		| excretion = Urine (90%)
	<!--Identifiers-->		<!--Identifiers-->
			| IUPHAR_ligand = 7304
	| CASNo_Ref = {{cascite}}
	| CAS_number_Ref = {{cascite|correct|??}}		| CAS_number_Ref = {{cascite|correct|??}}
	| CAS_number = 148-79-8		| CAS_number = 148-79-8
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	| ATC_supplemental = {{ATC|P02|CA02}} {{ATCvet|P52|AC10}}		| ATC_supplemental = {{ATC|P02|CA02}} {{ATCvet|P52|AC10}}
	| PubChem = 5430		| PubChem = 5430
	| DrugBank_Ref = {{drugbankcite|correct|drugbank}}		| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
	| DrugBank = <!-- blanked - oldvalue: APRD01252 -->		| DrugBank = DB00730
	| UNII_Ref = {{fdacite|changed|FDA}}		| UNII_Ref = {{fdacite|correct|FDA}}
	| UNII = N1Q45E87DT		| UNII = N1Q45E87DT
	| KEGG_Ref = {{keggcite|correct|kegg}}		| KEGG_Ref = {{keggcite|correct|kegg}}
	| KEGG = D00372		| KEGG = D00372
	| ChEMBL_Ref = {{ebicite|changed|EBI}}		| ChEMBL_Ref = {{ebicite|changed|EBI}}
	| ChEMBL = <!-- blanked - oldvalue: 625 -->		| ChEMBL = 625
			| NIAID_ChemDB = 007903
	| C=10 | H=7 | N=3 | S=1
			| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}
	| molecular_weight = 201.249 g/mol
			| ChemSpiderID = 5237
			| StdInChI_Ref = {{stdinchicite|changed|chemspider}}
			| StdInChI = 1S/C10H7N3S/c1-2-4-8-7(3-1)12-10(13-8)9-5-14-6-11-9/h1-6H,(H,12,13)
			| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}
			| StdInChIKey = WJCNZQLZVWNLKY-UHFFFAOYSA-N
			<!--Chemical data-->
			| C=10 | H=7 | N=3 | S=1
	| smiles = 1c2ccccc2nc1c3cscn3		| smiles = 1c2ccccc2nc1c3cscn3
	| density = 1.103		| density = 1.103
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	}}		}}
	'''Tiabendazole''' (], other names include '''TBZ''', '''thiabendazole''' and the trade names '''Mintezol''', '''Tresaderm''', and '''Arbotect''') is a ] and ].		'''Tiabendazole''' (], ]), also known as '''thiabendazole''' (], ]) or '''TBZ''' and the trade names Mintezol, Tresaderm, and Arbotect, is a preservative,<ref>{{Cite web|url=http://www.ivyroses.com/Define/E233|title=E233 : E Number : Preservative|website=www.ivyroses.com|language=en-GB|access-date=2018-08-28}}</ref> an antifungal agent, and an antiparasitic agent.
	==Uses==		== Uses ==
	===Fungicide===
	It is used primarily to control ], ], and other fungally caused diseases in fruits (e.g. ]) and vegetables; it is also used as a ] treatment for ].
			=== Preservative ===
	Use in treatment of ] has been reported.<ref name="pmid6766732">{{cite journal |author=Upadhyay MP, West EP, Sharma AP |title=Keratitis due to Aspergillus flavus successfully treated with thiabendazole |journal=Br J Ophthalmol |volume=64 |issue=1 |pages=30–2 |year=1980 |month=January |pmid=6766732 |pmc=1039343 |doi= 10.1136/bjo.64.1.30|url=http://bjo.bmj.com/cgi/pmidlookup?view=long&pmid=6766732}}</ref>
			Tiabendazole is used primarily to control ], ], and other fungal diseases in fruits (e.g. ]) and vegetables; it is also used as a ] treatment for ]. {{cn|date=December 2022}}
			Tiabendazole is also used as a ],<ref name="pmid853540">{{cite journal | vauthors = Rosenblum C | title = Non-drug-related residues in tracer studies | journal = Journal of Toxicology and Environmental Health | volume = 2 | issue = 4 | pages = 803–814 | date = March 1977 | pmid = 853540 | doi = 10.1080/15287397709529480 | bibcode = 1977JTEH....2..803R }}</ref><ref>{{cite book | vauthors = Sax NI | title = Dangerous Properties of Industrial Materials | volume = 1–3 | edition = 7th | location = New York, NY | publisher = Van Nostrand Reinhold | date = 1989 | page = 3251 }}</ref> a ] with ] E233 (] 233). For example, it is applied to ] to ensure freshness, and is a common ingredient in the ]es applied to the skins of ]s. It is not approved as a food additive in the EU,<ref>UK Food Standards Agency: {{cite web |url=http://www.food.gov.uk/safereating/chemsafe/additivesbranch/enumberlist |title=Current EU approved additives and their E Numbers |access-date=2011-10-27}}</ref> Australia and New Zealand.<ref>Australia New Zealand Food Standards Code{{cite web |url=http://www.comlaw.gov.au/Details/F2011C00827 |title=Standard 1.2.4 – Labelling of ingredients |date=8 September 2011 |access-date=2011-10-27}}</ref>
	===Parasiticide===
	As an antiparasitic, it is able to control ]s (such as ])<ref name="pmid15571478">{{cite journal |author=Igual-Adell R, Oltra-Alcaraz C, Soler-Company E, Sánchez-Sánchez P, Matogo-Oyana J, Rodríguez-Calabuig D |title=Efficacy and safety of ivermectin and thiabendazole in the treatment of strongyloidiasis |journal=Expert Opin Pharmacother |volume=5 |issue=12 |pages=2615–9 |year=2004 |month=December |pmid=15571478 |doi=10.1517/14656566.5.12.2615 |url=http://www.informapharmascience.com/doi/abs/10.1517/14656566.5.12.2615}}</ref>, ]s, and other ] species which attack wild animals, ] and humans. <ref name="pmid12031927">{{cite journal |author=Portugal R, Schaffel R, Almeida L, Spector N, Nucci M |title=Thiabendazole for the prophylaxis of strongyloidiasis in immunosuppressed patients with hematological diseases: a randomized double-blind placebo-controlled study |journal=Haematologica |volume=87 |issue=6 |pages=663–4 |year=2002 |month=June |pmid=12031927 |doi= |url=http://www.haematologica.org/cgi/pmidlookup?view=long&pmid=12031927}}</ref>
			Use in treatment of ] has been reported.<ref name="pmid6766732">{{cite journal | vauthors = Upadhyay MP, West EP, Sharma AP | title = Keratitis due to Aspergillus flavus successfully treated with thiabendazole | journal = The British Journal of Ophthalmology | volume = 64 | issue = 1 | pages = 30–32 | date = January 1980 | pmid = 6766732 | pmc = 1039343 | doi = 10.1136/bjo.64.1.30 }}</ref>
	==Pharmacodynamics / Mode of Action==
			It is also used in anti-fungal ]s as a mixture with ].{{cn|date=December 2022}}
	Inhibition of the mitochondrial helminth-specific enzyme, fumarate reductase, with possible interaction with endogenous quinone.<ref>Gilman, A.G., T.W. Rall, A.S. Nies and P. Taylor (eds.). Goodman and Gilman's The Pharmacological Basis of Therapeutics. 8th ed. New York, NY. Pergamon Press, 1990., p. 970</ref>
			=== Parasiticide ===
	==Other==
			As an antiparasitic, tiabendazole is able to control ]s (such as those causing ]),<ref name="pmid15571478">{{cite journal | vauthors = Igual-Adell R, Oltra-Alcaraz C, Soler-Company E, Sánchez-Sánchez P, Matogo-Oyana J, Rodríguez-Calabuig D | title = Efficacy and safety of ivermectin and thiabendazole in the treatment of strongyloidiasis | journal = Expert Opinion on Pharmacotherapy | volume = 5 | issue = 12 | pages = 2615–2619 | date = December 2004 | pmid = 15571478 | doi = 10.1517/14656566.5.12.2615 | url = http://www.informapharmascience.com/doi/abs/10.1517/14656566.5.12.2615 | url-status = dead | s2cid = 23721306 | archive-url = https://web.archive.org/web/20160306080701/http://informapharmascience.com/doi/abs/10.1517/14656566.5.12.2615 | archive-date = 2016-03-06 }}</ref> ]s, and other ] species which infect wild animals, ], and humans.<ref name="pmid12031927">{{cite journal | vauthors = Portugal R, Schaffel R, Almeida L, Spector N, Nucci M | title = Thiabendazole for the prophylaxis of strongyloidiasis in immunosuppressed patients with hematological diseases: a randomized double-blind placebo-controlled study | journal = Haematologica | volume = 87 | issue = 6 | pages = 663–664 | date = June 2002 | pmid = 12031927 | url = http://www.haematologica.org/cgi/pmidlookup?view=long&pmid=12031927 }}</ref> First approved for use in sheep in 1961 and horses in 1962, resistance to this drug was first found in '']'' in 1964, and then in the two other major small ruminant nematode parasites, '']'' and ''Trichostrongylus colubriformis.''<ref>{{Cite journal |last=Kaplan |first=Ray M. |date=October 2004 |title=Drug resistance in nematodes of veterinary importance: a status report |url=https://pubmed.ncbi.nlm.nih.gov/15363441/ |journal=Trends in Parasitology |volume=20 |issue=10 |pages=477–481 |doi=10.1016/j.pt.2004.08.001 |issn=1471-4922 |pmid=15363441}}</ref>
	Medicinally, thiabendazole is also a ], which means that it is used medicinally to bind metals in cases of metal poisoning, such as ], ] or ].
			=== Fungicide ===
	In dogs and cats thiabendazole is also used to treat ear infections.
			Tiabendazole acts as a fungicide through binding fungal tubulin. Resistant '']'' 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.<ref>{{Cite journal |last=Wang |first=C. C. |date=January 1984 |title=Parasite enzymes as potential targets for antiparasitic chemotherapy |url=https://pubmed.ncbi.nlm.nih.gov/6317859/ |journal=Journal of Medicinal Chemistry |volume=27 |issue=1 |pages=1–9 |doi=10.1021/jm00367a001 |issn=0022-2623 |pmid=6317859}}</ref>
			This chemical is also used as a pesticide, including to treat ].
	Thiabendazole is also used as a ]<ref name="pmid853540">{{cite journal
			<ref>{{cite web |title=Beech Leaf Disease |url=https://ag.umass.edu/landscape/fact-sheets/beech-leaf-disease |website=UMass Extension Landscape, Nursery and Urban Forestry Program |publisher=University of Massachusetts Amherst |access-date=30 July 2024}}</ref>
	|author=Rosenblum C
	|title=Non-drug-related residues in tracer studies
	|journal=Journal of Toxicology and Environmental Health
	|volume=2
	|issue=4
	|pages=803–14
	|year=1977
	|month=March
	|pmid=853540
	|doi=
	10.1080/15287397709529480|url=
	|issn=
	|accessdate=2009-06-21
	}}</ref><ref>Sax, N.I. Dangerous Properties of Industrial Materials. Vol 1-3 7th ed. New York, NY: Van Nostrand Reinhold, 1989., p. 3251</ref>, a ] with ] E233 (INS number 233). For example, it is applied to ] to ensure freshness, and is a common ingredient in the ]es applied to the skin of ]s. It is not approved for usage in the EU,<ref>UK Food Standards Agency: {{cite web |url=http://www.food.gov.uk/safereating/chemsafe/additivesbranch/enumberlist |title=Current EU approved additives and their E Numbers |accessdate=2011-10-27}}</ref> Australia and New Zealand<ref>Australia New Zealand Food Standards Code{{cite web |url=http://www.comlaw.gov.au/Details/F2011C00827 |title=Standard 1.2.4 - Labelling of ingredients |accessdate=2011-10-27}}</ref> or the USA.
	==Safety==		=== Other ===
			In dogs and cats, tiabendazole is used to treat ear infections.{{clarify|Infection by what type of organism? Parasite, bacteria, virus?|date=April 2019}}
	The substance appears to have a slight toxicity in higher doses, with effects such as liver and intestine disorder at high exposure in test animals (just below {{LD50}} level).{{Fact|date=June 2008}} Some reproductive disorders and decreasing weanling weight have been observed, also at high exposure. Effects on humans from use as drug includes 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.{{Fact|date=June 2008}} No mutagenic or carcinogenic effects have been shown.
			Tiabendazole is also a ], which means it is used medicinally to bind metals in cases of metal poisoning, such as ], ], or ] poisoning.{{medcn|date=April 2019}}
	==See also==
			== Research ==
			Genes responsible for the maintenance of cell walls in yeast have been shown to be responsible for ] 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.<ref>{{cite journal | vauthors = Cha HJ, Byrom M, Mead PE, Ellington AD, Wallingford JB, Marcotte EM | title = Evolutionarily repurposed networks reveal the well-known antifungal drug thiabendazole to be a novel vascular disrupting agent | journal = PLOS Biology | volume = 10 | issue = 8 | pages = e1001379 | date = August 2012 | pmid = 22927795 | pmc = 3423972 | doi = 10.1371/journal.pbio.1001379 | doi-access = free }}</ref>
			== Pharmacodynamics ==
			Tiabendazole works by inhibition of the mitochondrial, helminth-specific enzyme, ], with possible interaction with endogenous quinone.<ref>{{cite book | veditors = Gilman AG, Rall TW, Nies AS, Taylor P | title = Goodman and Gilman's The Pharmacological Basis of Therapeutics | edition = 8th | location = New York, NY | publisher = Pergamon Press | date = 1990 | page = 970}}</ref>
			== 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|date=June 2008}} 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|date=June 2008}} Carcinogenic effects have been shown at higher doses.<ref>{{cite web|title=Reregistration Eligibility Decision Thiabendazole |url=http://www.epa.gov/oppsrrd1/REDs/thiabendazole_red.pdf|publisher=Environmental Protection Agency|access-date=8 January 2013}}</ref>
			== Synthesis ==
			Intermediate aryl ] ('''2''') is prepared by ]-catalyzed addition of ] to the nitrile of 4-cyanothiazole ('''1''').<ref>{{Cite journal | doi = 10.1021/jo01012a061| title = Novel Preparation of Benzimidazoles from N-Arylamidines. New Synthesis of Thiabendazole | journal = The Journal of Organic Chemistry| volume = 30| pages = 259–261| year = 1965| vauthors = Grenda VJ, Jones RE, Gal G, Sletzinger M }}</ref><ref>{{cite patent | inventor = Sarett LH, Brown HD | title = Anthelmintic substituted benzimidazole compositions | country = US | number = 3336192 | gdate = 1967 | assign1 = ] }}</ref> The amidine ('''2''') is then converted to its ''N''-chloro derivative '''3''' with ] (NaOCl). Upon treatment with base, this undergoes a ] insertion reaction ('''4''') to produce tiabendazole ('''5''').
			]
			An alternative synthesis involves reacting 4-thiazolecarboxamide with ] in polyphosphoric acid.<ref>{{Cite journal | doi = 10.1021/ja01468a052| title = Antiparasitic Drugs. IV. 2-(4'-Thiazolyl)-Benzimidazole, A New Anthelmintic| journal = Journal of the American Chemical Society| volume = 83| issue = 7| pages = 1764–1765| year = 1961| vauthors = Brown HD, Matzuk AR, Ilves I, Peterson LH, Harris SA, Sarett LH, Egerton JR, Yakstis JJ, Campbell WC, Cuckler AC | display-authors = 6 }}</ref>
			===Derivatives===
			A number of ] of tiabendazole are also pharmaceutical drugs, including
			], ], ], ], ], and ].
			]<ref>{{cite patent | title = Anthelmintic 5-substituted aminobenzimidazoles | inventor = Hoff DR, Fisher MH |country= ZA |number= 6800351 | gdate = 1969 | assign1 = Merck and Co., Inc. }} Chemical Abstracts 72, 90461 (1970).</ref><ref>{{cite journal | vauthors = Hoff DR, Fisher MH, Bochis RJ, Lusi A, Waksmunski F, Egerton JR, Yakstis JJ, Cuckler AC, Campbell WC | display-authors = 6 | title = A new broad-spectrum anthelmintic: 2-(4-thiazolyl)-5-isopropoxycarbonylamino-benzimidazole | journal = Experientia | volume = 26 | issue = 5 | pages = 550–551 | date = May 1970 | pmid = 4245814 | doi = 10.1007/BF01898506 | s2cid = 26567527 }}</ref>]]
			== See also ==
	* ]		* ]
	* ]		* ]
	* ]
	==References==		== References ==
	{{reflist}}		{{reflist}}
			== External links ==
	*		*
	*		*
	{{Antifungals}}		{{Antifungals}}
	{{Anthelmintics}}		{{Anthelmintics}}
			{{Authority control}}
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