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Identification
NameDiloxanide
Accession NumberDB08792
Typesmall molecule
Groupsapproved
Description

Diloxanide furoate is an anti-protozoal drug used in the treatment of Entamoeba histolytica and some other protozoal infections. Although it is not currently approved for use in the United States, it was approved by a CDC study in the treatment of 4,371 cases of Entamoeba histolytica from 1977 to 1990.

Structure
Thumb
Synonyms
SynonymLanguageCode
Diloxanide furoateNot AvailableNot Available
SaltsNot Available
Brand namesNot Available
Brand mixturesNot Available
Categories
CAS number3736-81-0
WeightAverage: 328.147
Monoisotopic: 327.006513259
Chemical FormulaC14H11Cl2NO4
InChI KeyInChIKey=BDYYDXJSHYEDGB-UHFFFAOYSA-N
InChI
InChI=1S/C14H11Cl2NO4/c1-17(13(18)12(15)16)9-4-6-10(7-5-9)21-14(19)11-3-2-8-20-11/h2-8,12H,1H3
IUPAC Name
4-(2,2-dichloro-N-methylacetamido)phenyl furan-2-carboxylate
SMILES
CN(C(=O)C(Cl)Cl)C1=CC=C(OC(=O)C2=CC=CO2)C=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassBenzene and Substituted Derivatives
SubclassPhenol Esters
Direct parentPhenol Esters
Alternative parentsAnilides; Furoic Acid Derivatives; Phenol Ethers; Alkyl Aryl Ethers; Tertiary Carboxylic Acid Amides; Tertiary Amines; Carboxylic Acid Esters; Carboxylic Acids; Enolates; Polyamines; Alkyl Chlorides; Organochlorides
Substituentsphenol ether; furoate; alkyl aryl ether; tertiary carboxylic acid amide; furan; carboxamide group; tertiary amine; carboxylic acid ester; polyamine; carboxylic acid; enolate; carboxylic acid derivative; ether; organohalogen; organochloride; amine; alkyl halide; alkyl chloride; organonitrogen compound
Classification descriptionThis compound belongs to the phenol esters. These are aromatic compounds containing a benzene ring substituted by an hydroxyl group and an ester group.
Pharmacology
IndicationDiloxanide is used alone as a primary agent in the treatment of asymptomatic (cyst passers) intestinal amebiasis caused by Entamoeba histolytica. Diloxanide may also be used concurrently, or sequentially, with other agents such as the nitroimidazoles (eg. metronidazole) in the treatment of invasive or extraintestinal forms of amebiasis.
PharmacodynamicsDiloxanide is a luminal amebicide, however the mechanism of action of diloxanide is unknown. Diloxanide destroys the trophozoites of E. histolytica that eventually form into cysts. The cysts are then excreted by persons infected with asymptomatic amebiasis. Diloxanide furoate is a prodrug, and is hydrolyzed in the gastrointestinal tract to produce diloxanide, the active ingredient.
Mechanism of actionUnknown. Diloxanide may inhibit protein synthesis.
AbsorptionBioavailability is 90% (in diloxanide parental form), however diloxanide furoate is slowly absorbed from the gastrointestinal tract.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hydrolyzed to furoic acid and diloxanide, which undergoes extensive glucuronidation (99% of diloxanide occurs as glucuronide and 1% as free diloxanide in the systemic circulation).

Route of eliminationRenal (90%, rapidly excreted as glucuronide metabolite). 10% is excreted in the feces as diloxanide.
Half life3 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Protozoa
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.9454
Blood Brain Barrier + 0.9784
Caco-2 permeable + 0.5558
P-glycoprotein substrate Non-substrate 0.8705
P-glycoprotein inhibitor I Non-inhibitor 0.9364
P-glycoprotein inhibitor II Non-inhibitor 0.7636
Renal organic cation transporter Non-inhibitor 0.8958
CYP450 2C9 substrate Non-substrate 0.7021
CYP450 2D6 substrate Non-substrate 0.8229
CYP450 3A4 substrate Substrate 0.585
CYP450 1A2 substrate Non-inhibitor 0.9045
CYP450 2C9 substrate Non-inhibitor 0.907
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9025
CYP450 3A4 substrate Non-inhibitor 0.8944
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.5266
Ames test AMES toxic 0.538
Carcinogenicity Non-carcinogens 0.7816
Biodegradation Not ready biodegradable 0.8478
Rat acute toxicity 2.2608 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9924
hERG inhibition (predictor II) Non-inhibitor 0.9271
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
logP2.24DUTTA,H ET AL. (1988)
Predicted Properties
PropertyValueSource
water solubility3.82e-02 g/lALOGPS
logP3.33ALOGPS
logP3.08ChemAxon
logS-3.9ALOGPS
pKa (strongest acidic)13.09ChemAxon
pKa (strongest basic)-4.7ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count2ChemAxon
hydrogen donor count0ChemAxon
polar surface area59.75ChemAxon
rotatable bond count5ChemAxon
refractivity78.21ChemAxon
polarizability30.28ChemAxon
number of rings2ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterYesChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. McAuley JB, Herwaldt BL, Stokes SL, Becher JA, Roberts JM, Michelson MK, Juranek DD: Diloxanide furoate for treating asymptomatic Entamoeba histolytica cyst passers: 14 years’ experience in the United States. Clin Infect Dis. 1992 Sep;15(3):464-8. Pubmed. Williams and T.L. Lemke, #Foye’s Principles of Medicinal Chemistry (fifth ed), Lippincott Williams & Wilkins, Baltimore (2002), p. 872.www.ncbi.nlm.nih.gov/pubmed/1520794
External Links
ResourceLink
ChemSpider18400
PharmGKBPA165958413
Drugs.comhttp://www.drugs.com/mmx/diloxanide-furoate.html
WikipediaDiloxanide_furoate
ATC CodesP01AC01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available
Comments
Drug created on September 20, 2010 08:58 / Updated on September 16, 2013 18:11