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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
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
CAS number3736-81-0
WeightAverage: 328.147
Monoisotopic: 327.006513259
Chemical FormulaC14H11Cl2NO4
InChI KeyBDYYDXJSHYEDGB-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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenol esters. These are aromatic compounds containing a benzene ring substituted by a hydroxyl group and an ester group.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenol esters
Direct ParentPhenol esters
Alternative Parents
Substituents
  • Phenol ester
  • Furoate
  • Heteroaromatic compound
  • Tertiary carboxylic acid amide
  • Furan
  • Tertiary amine
  • Carboxylic acid ester
  • Carboxamide group
  • Oxacycle
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Carbonyl group
  • Amine
  • Alkyl halide
  • Alkyl chloride
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
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
PropertyValueProbability
Human Intestinal Absorption+0.9454
Blood Brain Barrier+0.9784
Caco-2 permeable+0.5558
P-glycoprotein substrateNon-substrate0.8705
P-glycoprotein inhibitor INon-inhibitor0.9364
P-glycoprotein inhibitor IINon-inhibitor0.7636
Renal organic cation transporterNon-inhibitor0.8958
CYP450 2C9 substrateNon-substrate0.7021
CYP450 2D6 substrateNon-substrate0.8229
CYP450 3A4 substrateSubstrate0.585
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 substrateNon-inhibitor0.907
CYP450 2D6 substrateNon-inhibitor0.9231
CYP450 2C19 substrateNon-inhibitor0.9025
CYP450 3A4 substrateNon-inhibitor0.8944
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5266
Ames testAMES toxic0.538
CarcinogenicityNon-carcinogens0.7816
BiodegradationNot ready biodegradable0.8478
Rat acute toxicity2.2608 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9924
hERG inhibition (predictor II)Non-inhibitor0.9271
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 Solubility0.0382 mg/mLALOGPS
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 Area59.75 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity78.21 m3·mol-1ChemAxon
Polarizability30.28 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
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
ATC CodesP01AC01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available
Comments
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Drug created on September 20, 2010 08:58 / Updated on September 16, 2013 18:11