BITHIONOL

Details

Stereochemistry	ACHIRAL
Molecular Formula	C12H6Cl4O2S
Molecular Weight	356.052
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC1=C(SC2=C(O)C(Cl)=CC(Cl)=C2)C=C(Cl)C=C1Cl

InChI

InChIKey=JFIOVJDNOJYLKP-UHFFFAOYSA-N

InChI=1S/C12H6Cl4O2S/c13-5-1-7(15)11(17)9(3-5)19-10-4-6(14)2-8(16)12(10)18/h1-4,17-18H

HIDE SMILES / InChI

Description
Sources: http://onlinelibrary.wiley.com/doi/10.1002/3527600418.mb9718kske0009/pdf
Curator's Comment: description was created based on several sources, including https://www.drugbank.ca/drugs/DB04813 | https://goo.gl/7Qnwi7 | https://www.ncbi.nlm.nih.gov/pubmed/26961873 | https://www.ncbi.nlm.nih.gov/pubmed/5567745 | https://www.ncbi.nlm.nih.gov/pubmed/23990907

Bithionol is a synthetic sulfanediyl-bis-dichlorphenol), potent photosensitizer with the potential to cause serious skin disorders, formerly marketed as an active ingredient in various topical drug products. Bithionol has antibacterial and anthelmintic properties along with algaecide activity. Bithionol has been shown to be a potent inhibitor of soluble adenylyl cyclase (sAC, Adenylate cyclase type 10 ), an intracellular enzyme important in the catalysis of ATP to cAMP. Bithionol is the first known sAC inhibitor to act through the bicarbonate binding site via a mostly allosteric mechanism. Bithionol is used for treatment of tapeworm infections of dogs, cats, and poultry and for tapeworm and rumen fluke infections of sheep, horses, cattle, and goats.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Adenylate cyclase type 10 2 Target ID: CHEMBL5854 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26961873	Inhibitor 8297		4.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Intestinal capillariasis 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/5567745	Primary		Not Provided 504	Actamer Approved Use Unknown

Doses

Dose	Population	Adverse events
1 % 1 times / day single, topical Studied dose Dose: 1 %, 1 times / day Route: topical Route: single Dose: 1 %, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13826897/	healthy, 22 years n = 1 Health Status: healthy Age Group: 22 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/13826897/	Other AEs: Contact dermatitis... Other AEs: Contact dermatitis Sources: https://pubmed.ncbi.nlm.nih.gov/13826897/
2.4 g 1 times / day multiple, oral Studied dose Dose: 2.4 g, 1 times / day Route: oral Route: multiple Dose: 2.4 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/5567745/	unhealthy, mean age 35 years n = 8 Health Status: unhealthy Condition: intestinal capillariasis Age Group: mean age 35 years Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/5567745/	Other AEs: Abdominal pain aggravated... Other AEs: Abdominal pain aggravated (37.5%) Sources: https://pubmed.ncbi.nlm.nih.gov/5567745/

AEs

AE	Significance	Dose	Population
Contact dermatitis		1 % 1 times / day single, topical Studied dose Dose: 1 %, 1 times / day Route: topical Route: single Dose: 1 %, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13826897/	healthy, 22 years n = 1 Health Status: healthy Age Group: 22 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/13826897/
Abdominal pain aggravated	37.5%	2.4 g 1 times / day multiple, oral Studied dose Dose: 2.4 g, 1 times / day Route: oral Route: multiple Dose: 2.4 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/5567745/	unhealthy, mean age 35 years n = 8 Health Status: unhealthy Condition: intestinal capillariasis Age Group: mean age 35 years Sex: M+F Population Size: 8 Sources: https://pubmed.ncbi.nlm.nih.gov/5567745/

Sourcing

Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B3-046256	http://www.3bsc.com/index/pro_info.php?id=82855
AHH Chemical co.,ltd	MT-30989	http://www.ahhchemical.com/product/MT-30989.html
Ambeed	A289469	https://www.ambeed.com/products/6385-58-6.html
Ambinter	Amb10843662	http://www.ambinter.com/reference/10843662
Angel Pharmatech	AG260602	http://www.angelpharmatech.com/6385-58-6.html
Aurora Fine Chemicals LLC	A17.909.556	http://online.aurorafinechemicals.com/info?ID=A17.909.556
BLD Pharm	BD64694	http://www.bldpharm.com/products/6385-58-6.html
BOC Sciences	6385-58-6	https://www.bocsci.com/2-2-thiobis-4-6-dichlorophenol-disodium-salt-cas-6385-58-6-item-30849.html
Chemspace	CSSB00102585214	https://chem-space.com/CSSB00102585214
Combi-Blocks	QE-0841	http://www.combi-blocks.com/cgi-bin/find.cgi?QE-0841
Finetech	FT-0708482	http://www.finetechnology-ind.com/prod/detail/pub/6385-58-6.html
Sigma-Aldrich	CDS000488_ALDRICH	https://www.sigmaaldrich.com/catalog/product/aldrich/cds000488?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
TCI (Tokyo Chemical Industry)	T0406	http://www.tcichemicals.com/eshop/en/us/commodity/T0406/index.html
abcr GmbH	AB142463	http://www.abcr.de/shop/en/AB142463
eNovation Chemicals	D108017	https://www.enovationchem.com/ProductDetails.asp?ProductID=D108017

PubMed

Title	Date	PubMed
Treatment of experimental pneumocystosis: review of 7 years of experience and development of a new system for classifying antimicrobial drugs.	1992 Sep	1416885
Efficacy of 101 antimicrobials and other agents on the development of Cryptosporidium parvum in vitro.	1996 Dec	9039272
Hydrogen peroxide induced stress in human keratinocytes and its effect on bithionol toxicity.	2001 Aug-Oct	11566576
Paragonimiasis in Yongjia County, Zhejiang Province, China: clinical, parasitological and karyotypic studies on Paragonimus westermani.	2001 Dec	12041551
[Fasciola hepatica. study of a series of 37 patients].	2001 Oct	11674955
[Antiparasitic treatments in pregnant women and in children in 2003].	2003	14763305
[Fascioliasis: diagnosis, epidemiology and treatment].	2003 Apr-Jun	15127652
Spectrum of cross-photosensitization in 18 consecutive patients with contact photoallergy to ketoprofen: associated photoallergies to non-benzophenone-containing molecules.	2003 Mar	12755728
Sonographic findings of hepatic lesions in human fascioliasis.	2003 Sep	12923880
Fasciola hepatica infestation as a very rare cause of extrahepatic cholestasis.	2004 Oct 15	15378799
A native 13-kDa fatty acid binding protein from the liver fluke Fasciola hepatica.	2004 Sep 24	15374624
Search of chemical scaffolds for novel antituberculosis agents.	2005 Apr	15809316
Acute toxicity to freshwater organisms of antiparasitic drugs for veterinary use.	2005 Feb	15712325
Infection with Fasciola hepatica.	2005 Nov	16216098
Contractile activity and motility responses of the dog heartworm Dirofilaria immitis to classical anthelmintics and other compounds.	2005 Nov 25	16076531
Kinetic, inhibition and structural studies on 3-oxoacyl-ACP reductase from Plasmodium falciparum, a key enzyme in fatty acid biosynthesis.	2006 Jan 15	16225460
Fasciola hepatica infection: clinical and computerized tomographic findings of ten patients.	2006 Mar	16830276
Indirect evidence of ectopic pancreatic fascioliasis in a human.	2006 Oct	16928233
Pharmacological activation and inhibition of Slack (Slo2.2) channels.	2006 Sep	16876206
Treatment of helminth co-infection in individuals with HIV-1: A systematic review of the literature.	2007 Dec 19	18160978
Induction of keratinocyte apoptosis by photosensitizing chemicals plus UVA.	2007 Feb	17141480
Evaluation of bithionol as a bath treatment for amoebic gill disease caused by Neoparamoeba spp.	2007 Mar 31	17129675
Slack and Slick K(Na) channels regulate the accuracy of timing of auditory neurons.	2007 Mar 7	17344399
An evaluation of the effects of photoactivation of bithionol, amiodarone and chlorpromazine on human keratinocytes in vitro.	2007 Oct	18001169
In Vitro Anthelmintic Activity of Baliospermum montanum Muell. Arg roots.	2008 Jan	20390101
The old and new therapeutic approaches to the treatment of giardiasis: where are we?	2009	19707415
Novel inhibitors complexed with glutamate dehydrogenase: allosteric regulation by control of protein dynamics.	2009 Aug 21	19531491
Prediction of pharmacological and xenobiotic responses to drugs based on time course gene expression profiles.	2009 Dec 2	19956587
Combining chemical genomics screens in yeast to reveal spectrum of effects of chemical inhibition of sphingolipid biosynthesis.	2009 Jan 14	19144191
Drug discovery for schistosomiasis: hit and lead compounds identified in a library of known drugs by medium-throughput phenotypic screening.	2009 Jul 14	19597541
Diphyllobothriasis associated with eating raw pacific salmon.	2009 Jun	19523283
[Phosphatases of cestodes Bothriocephalus scorpii and influence of some anthelmintic preparations on activities of these enzymes].	2009 Mar-Apr	19505013
Evaluation of marked rise in fecal egg output after bithionol administration to horse and its application as a diagnostic marker for equine Anoplocephala perfoliata infection.	2009 May	19498288
Further development of bithionol therapy as a treatment for amoebic gill disease in Atlantic salmon, Salmo salar L.	2009 May	19243491
Molecular cloning, expression and characterization of a novel mouse SULT6 cytosolic sulfotransferase.	2009 Sep	19505954
A 20-year analysis of previous and emerging allergens that elicit photoallergic contact dermatitis.	2010 Apr	20163891
Determination of bithionol, bromophen, nitroxynil, oxyclozanide, and tribromsalan in milk with liquid chromatography coupled with tandem mass spectrometry.	2010 Jul-Aug	20922970
Endoscopic management of biliary fascioliasis: a case report.	2010 Mar 6	20205932
Identification of known drugs that act as inhibitors of NF-kappaB signaling and their mechanism of action.	2010 May 1	20067776
In vitro toxicity of bithionol and bithionol sulphoxide to Neoparamoeba spp., the causative agent of amoebic gill disease (AGD).	2010 Sep 17	21133325
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.	2011 Jul 14	21599003
An improved thyroid hormone reporter assay to determine the thyroid hormone-like activity of amiodarone, bithionol, closantel and rafoxanide.	2012 Jan 5	22015988

Patents

Sample Use Guides

In Vivo Use Guide

After oral administration of single bithionol doses of 30 mg/kg body weight to healthy test persons (fasting, number not stated) no effects were observed, single oral doses of 50 mg/kg body weight caused diarrhoea and 150 mg/kg body weight prolonged diarrhoea, nausea and abdominal pains

Route of Administration: Oral

In Vitro Use Guide

Cytotoxic effect of BT (Bithionol) was evaluated against a panel of ovarian cancer cell lines (A2780 & A2780-CDDP OVACAR-3, SKOV-3, IGROV-1, and IGROV-1CDDP). A 20 mM stock of BT was prepared in DMSO and all the working dilutions were prepared in DMEM media. Ovarian cancer cell lines (5 × 103 cells/well) were plated into 96-well flat bottom plates (Corning, Inc., Corning, NY) and incubated for overnight. Cells were treated with different concentrations of BT ranging from 0.178 μM to 400 μM and further incubated for 48 hrs or 72 hrs. At least 4–6 hrs before the end of treatment time, presto blue reagent was added and incubated for total of 48 or 72 hrs and fluorescence measured (540 nm excitation/590 nm emissions). DMSO concentration was corrected to 1% in all wells.

Name

Type

Language

BITHIONOL

Official Name

English

Bithionol [WHO-DD]

Common Name

English

bithionol [INN]

Common Name

English

BITHIN

Brand Name

English

BITHIONOL [HSDB]

Common Name

English

BITHIONOL [MART.]

Common Name

English

NSC-47129

Code

English

BITHIONOL [MI]

Common Name

English

LOROTHIDOL

Brand Name

English

BITHIONOL [JAN]

Common Name

English

2,2'-THIOBIS(4,6-DICHLOROPHENOL)

Systematic Name

English

Classification Tree Code System Code

WHO-ATC

P02BX01