Diloxanide

Identification

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Name
Diloxanide
Accession Number
DB08792
Type
Small Molecule
Groups
Experimental
Description

Diloxanide (as 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
3D
Similar Structures
Synonyms
Not Available
Categories
UNII
89134SCM7M
CAS number
579-38-4
Weight
Average: 234.08
Monoisotopic: 233.0010339
Chemical Formula
C9H9Cl2NO2
InChI Key
GZZZSOOGQLOEOB-UHFFFAOYSA-N
InChI
InChI=1S/C9H9Cl2NO2/c1-12(9(14)8(10)11)6-2-4-7(13)5-3-6/h2-5,8,13H,1H3
IUPAC Name
2,2-dichloro-N-(4-hydroxyphenyl)-N-methylacetamide
SMILES
CN(C(=O)C(Cl)Cl)C1=CC=C(O)C=C1

Pharmacology

Indication

Diloxanide 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.

Pharmacodynamics

Diloxanide 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 action

Unknown. Diloxanide may inhibit protein synthesis.

Absorption

Bioavailability is 90% (in diloxanide parental form), however diloxanide furoate is slowly absorbed from the gastrointestinal tract.

Volume of distribution
Not Available
Protein binding
Not 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 elimination

Renal (90%, rapidly excreted as glucuronide metabolite). 10% is excreted in the feces as diloxanide.

Half life

3 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Protozoa
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  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:1520794]
External Links
PubChem Compound
11367
PubChem Substance
99445263
ChemSpider
10889
ChEMBL
CHEMBL2103768
PharmGKB
PA165958413
Drugs.com
Drugs.com Drug Page
Wikipedia
Diloxanide_furoate
ATC Codes
P01AC01 — Diloxanide

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP2.24DUTTA,H ET AL. (1988)
Predicted Properties
PropertyValueSource
Water Solubility2.31 mg/mLALOGPS
logP2.01ALOGPS
logP2.05ChemAxon
logS-2ALOGPS
pKa (Strongest Acidic)9.39ChemAxon
pKa (Strongest Basic)-5.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area40.54 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity55.99 m3·mol-1ChemAxon
Polarizability20.9 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
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 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-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
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as anilides. These are organic heterocyclic compounds derived from oxoacids RkE(=O)l(OH)m (l not 0) by replacing an OH group by the NHPh group or derivative formed by ring substitution.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Anilides
Direct Parent
Anilides
Alternative Parents
1-hydroxy-2-unsubstituted benzenoids / Tertiary carboxylic acid amides / Organopnictogen compounds / Organonitrogen compounds / Organochlorides / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds / Alkyl chlorides
Substituents
Anilide / 1-hydroxy-2-unsubstituted benzenoid / Phenol / Tertiary carboxylic acid amide / Carboxamide group / Carboxylic acid derivative / Alkyl chloride / Hydrocarbon derivative / Organic oxide / Organopnictogen compound
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available

Drug created on September 20, 2010 08:58 / Updated on November 02, 2018 06:54