Identification

Name
Tioconazole
Accession Number
DB01007  (APRD01262)
Type
Small Molecule
Groups
Approved
Description

Tioconazole is an antifungal medication of the Imidazole class used to treat infections caused by a fungus or yeast. Tioconazole topical (skin) preparations are also available for ringworm, jock itch, athlete's foot, and tinea versicolor or "sun fungus". Tioconazole interacts with 14-alpha demethylase, a cytochrome P-450 enzyme that converts lanosterol to ergosterol, an essential component of the yeast membrane. In this way, tioconazole inhibits ergosterol synthesis, resulting in increased cellular permeability.

Structure
Thumb
Synonyms
  • Tioconazol
  • Tioconazole
  • Tioconazolum
Product Ingredients
IngredientUNIICASInChI Key
Tioconazole hydrochlorideT1QKM21KYB61675-64-7UKQXXGSDDSCAHA-UHFFFAOYSA-N
Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CareOne Tioconazole 1Ointment6.5 g/100gVaginalAmerican Sales Company2008-01-07Not applicableUs
Equaline Tioconazole 1Ointment6.5 g/100gVaginalSupervalu2016-03-08Not applicableUs
Equate tioconazole 1 dayOintment6.5 g/100gVaginalWalmart Stores2007-11-01Not applicableUs
Good Neighbor Pharmacy Tioconazole 1Ointment6.5 g/100gVaginalAmerisource Bergen2008-02-20Not applicableUs
Gynecure External Cream 1% (refill)Cream1 %TopicalPfizer Canada Inc., Consumer Healthcare DivisionNot applicableNot applicableCanada
Gynecure Vaginal Ointment 6.5% W/wOintment6.5 %VaginalPfizer Canada Inc., Consumer Healthcare Division1995-12-312002-11-11Canada
Gynecure Vaginal Ovule 300mgSuppository300 mgVaginalPfizer Canada Inc., Consumer Healthcare Division1995-12-312002-08-06Canada
Healthy Accents Tioconazole 1Ointment6.5 g/100gVaginalDza Brands,2008-04-06Not applicableUs
Image Essentials Tioconazole TreatmentOintment6.5 g/100gVaginalKmart Corporation2014-12-262018-10-26Us
Leader TiconazoleOintment6.5 g/100gVaginalCardinal Health2018-04-20Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Gynecure Com.pk.vag Ont6.5%vulvar Crm1% W/wTioconazole (1 %) + Tioconazole (6.5 %)Cream; OintmentTopical; VaginalPfizer Canada Inc., Consumer Healthcare Division1995-12-311997-08-12Canada
Gynecure Com.pk.vag Ont6.5%vulvar Crm1% W/wTioconazole (1 %) + Tioconazole (6.5 %)Cream; OintmentTopical; VaginalPfizer Canada Inc., Consumer Healthcare Division1995-12-311997-08-12Canada
Gynecure Com.pk.vag Ovule300mg Vulv.crm1%w/wTioconazole (1 %) + Tioconazole (300 mg)Cream; SuppositoryTopical; VaginalPfizer Canada Inc., Consumer Healthcare Division1995-12-311997-08-12Canada
Gynecure Com.pk.vag Ovule300mg Vulv.crm1%w/wTioconazole (1 %) + Tioconazole (300 mg)Cream; SuppositoryTopical; VaginalPfizer Canada Inc., Consumer Healthcare Division1995-12-311997-08-12Canada
Gynecure Tandempk.vag Ont6.5%/vulv.crm1%-w/wTioconazole (1 %) + Tioconazole (6.5 %)Cream; OintmentTopical; VaginalPfizer Canada Inc., Consumer Healthcare Division1997-03-272002-11-11Canada
Gynecure Tandempk.vag Ont6.5%/vulv.crm1%-w/wTioconazole (1 %) + Tioconazole (6.5 %)Cream; OintmentTopical; VaginalPfizer Canada Inc., Consumer Healthcare Division1997-03-272002-11-11Canada
Gynecure Tandempk.vag Ov.300mg/vulv.crm1%w/wTioconazole (1 %) + Tioconazole (300 mg)Cream; SuppositoryTopical; VaginalPfizer Canada Inc., Consumer Healthcare Division1996-12-022002-11-11Canada
Gynecure Tandempk.vag Ov.300mg/vulv.crm1%w/wTioconazole (1 %) + Tioconazole (300 mg)Cream; SuppositoryTopical; VaginalPfizer Canada Inc., Consumer Healthcare Division1996-12-022002-11-11Canada
International/Other Brands
GyneCure / Monistat 1 / Trosyd / Trosyl / Vagistat-1
Categories
UNII
S57Y5X1117
CAS number
65899-73-2
Weight
Average: 387.711
Monoisotopic: 385.981416859
Chemical Formula
C16H13Cl3N2OS
InChI Key
QXHHHPZILQDDPS-UHFFFAOYSA-N
InChI
InChI=1S/C16H13Cl3N2OS/c17-12-1-2-13(14(18)7-12)15(8-21-5-4-20-10-21)22-9-11-3-6-23-16(11)19/h1-7,10,15H,8-9H2
IUPAC Name
1-{2-[(2-chlorothiophen-3-yl)methoxy]-2-(2,4-dichlorophenyl)ethyl}-1H-imidazole
SMILES
ClC1=C(COC(CN2C=CN=C2)C2=C(Cl)C=C(Cl)C=C2)C=CS1

Pharmacology

Indication

For the local treatment of vulvovaginal candidiasis (moniliasis).

Associated Conditions
Pharmacodynamics

Tioconazole is a broad-spectrum imidazole antifungal agent that inhibits the growth of human pathogenic yeasts. Tioconazole exhibits fungicidal activity in vitro against Candida albicans, other species of the genus Candida, and against Torulopsis glabrata. Tioconazole prevents the growth and function of some fungal organisms by interfering with the production of substances needed to preserve the cell membrane. This drug is effective only for infections caused by fungal organisms. It will not work for bacterial or viral infections.

Mechanism of action

Tioconazole interacts with 14-α demethylase, a cytochrome P-450 enzyme that converts lanosterol to ergosterol, an essential component of the yeast membrane. In this way, tioconazole inhibits ergosterol synthesis, resulting in increased cellular permeability. Tioconazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms and the uptake of purine, impair triglyceride and/or phospholipid biosynthesis, and inhibit the movement of calcium and potassium ions across the cell membrane by blocking the ion transport pathway known as the Gardos channel.

TargetActionsOrganism
ALanosterol 14-alpha demethylase
antagonist
Yeast
ULanosterol 14-alpha demethylase
inhibitor
Human
Absorption

Systemic absorption following a single intravaginal application of tioconazole in nonpregnant patients is negligible.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Orally administered tioconazole is extensively metabolized. The major metabolites are glucuronide conjugates.

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Symptoms of overdose include erythema, stinging, blistering, peeling, edema, pruritus, urticaria, burning, and general irritation of the skin, and cramps.

Affected organisms
  • Yeast and other fungi
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
No interactions found.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015142
KEGG Drug
D00890
KEGG Compound
C08082
PubChem Compound
5482
PubChem Substance
46508604
ChemSpider
5282
BindingDB
50370218
ChEBI
77898
ChEMBL
CHEMBL1200438
Therapeutic Targets Database
DAP001268
PharmGKB
PA164746156
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Tioconazole
ATC Codes
G01AF08 — TioconazoleG01AF20 — Combinations of imidazole derivativesD01AC07 — Tioconazole
AHFS Codes
  • 84:04.08.08 — Azoles
FDA label
Download (784 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Pfizer laboratories div pfizer inc
  • L perrigo co
  • Novartis consumer health inc
Packagers
  • Johnson & Johnson Healthcare
  • Novartis AG
  • Walgreen Co.
Dosage forms
FormRouteStrength
Cream; ointmentTopical; Vaginal
Cream; suppositoryTopical; Vaginal
OintmentVaginal6.5 %
SuppositoryVaginal300 mg
OintmentVaginal6.5 g/100g
OintmentTopical300 mg/1g
OintmentVaginal65 mg/1g
CreamTopical1 %
CreamTopical10 mg
OintmentVaginal300 mg/1
Prices
Unit descriptionCostUnit
Monistat-Derm 2% Cream 28.35 gm Tube41.99USD tube
Monistat-Derm 2% Cream 15 gm Tube32.0USD tube
Monistat 1 combination pack16.81USD each
Monistat 1 6.5% ointment3.6USD g
Vagistat-1 6.5% ointment3.6USD g
Tioconazole 1 6.5% ointment1.75USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP4.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0165 mg/mLALOGPS
logP4.86ALOGPS
logP5.3ChemAxon
logS-4.4ALOGPS
pKa (Strongest Basic)6.77ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area27.05 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity94.53 m3·mol-1ChemAxon
Polarizability36.84 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.966
Blood Brain Barrier+0.9814
Caco-2 permeable+0.5812
P-glycoprotein substrateNon-substrate0.5819
P-glycoprotein inhibitor INon-inhibitor0.911
P-glycoprotein inhibitor IINon-inhibitor0.5295
Renal organic cation transporterInhibitor0.5164
CYP450 2C9 substrateNon-substrate0.8248
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.7558
CYP450 1A2 substrateInhibitor0.946
CYP450 2C9 inhibitorInhibitor0.8757
CYP450 2D6 inhibitorInhibitor0.9032
CYP450 2C19 inhibitorInhibitor0.926
CYP450 3A4 inhibitorInhibitor0.8406
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9934
Ames testNon AMES toxic0.8092
CarcinogenicityNon-carcinogens0.8543
BiodegradationNot ready biodegradable0.9869
Rat acute toxicity2.7335 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7187
hERG inhibition (predictor II)Inhibitor0.6506
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
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-000i-0009000000-2827a77fbda828e7453e
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-000i-0009000000-27b855fca59ed08acb85
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-001i-0903000000-30ef91f27453208dd584
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-001i-0900000000-2ed7f788cac071d871e4
LC-MS/MS Spectrum - LC-ESI-QQ , positiveLC-MS/MSsplash10-001i-0900000000-94a2a2533441e3179663
LC-MS/MS Spectrum - LC-ESI-IT , positiveLC-MS/MSsplash10-001i-0900000000-fa59d0317db7f93d6c2a
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0019-1619000000-7bfbe2de2c4aa4e6cd39

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzylethers. These are aromatic ethers with the general formula ROCR' (R = alkyl, aryl; R'=benzene).
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzylethers
Direct Parent
Benzylethers
Alternative Parents
Dichlorobenzenes / N-substituted imidazoles / Aryl chlorides / Thiophenes / Heteroaromatic compounds / Dialkyl ethers / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organochlorides
show 1 more
Substituents
Benzylether / 1,3-dichlorobenzene / Chlorobenzene / Halobenzene / Aryl chloride / Aryl halide / N-substituted imidazole / Azole / Heteroaromatic compound / Thiophene
show 14 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
imidazoles, thiophenes, ether, dichlorobenzene (CHEBI:77898)

Targets

Kind
Protein
Organism
Yeast
Pharmacological action
Yes
Actions
Antagonist
General Function
Sterol 14-demethylase activity
Specific Function
Catalyzes C14-demethylation of lanosterol which is critical for ergosterol biosynthesis. It transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol.
Gene Name
ERG11
Uniprot ID
P10613
Uniprot Name
Lanosterol 14-alpha demethylase
Molecular Weight
60674.965 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Ballard SA, Lodola A, Tarbit MH: A comparative study of 1-substituted imidazole and 1,2,4-triazole antifungal compounds as inhibitors of testosterone hydroxylations catalysed by mouse hepatic microsomal cytochromes P-450. Biochem Pharmacol. 1988 Dec 15;37(24):4643-51. [PubMed:3202901]
  3. Fliri AF, Loging WT, Thadeio PF, Volkmann RA: Biological spectra analysis: Linking biological activity profiles to molecular structure. Proc Natl Acad Sci U S A. 2005 Jan 11;102(2):261-6. Epub 2004 Dec 29. [PubMed:15625110]
  4. Bellamine A, Lepesheva GI, Waterman MR: Fluconazole binding and sterol demethylation in three CYP51 isoforms indicate differences in active site topology. J Lipid Res. 2004 Nov;45(11):2000-7. Epub 2004 Aug 16. [PubMed:15314102]
  5. Guinea J, Sanchez-Somolinos M, Cuevas O, Pelaez T, Bouza E: Fluconazole resistance mechanisms in Candida krusei: the contribution of efflux-pumps. Med Mycol. 2006 Sep;44(6):575-8. [PubMed:16966178]
  6. Chau AS, Chen G, McNicholas PM, Mann PA: Molecular basis for enhanced activity of posaconazole against Absidia corymbifera and Rhizopus oryzae. Antimicrob Agents Chemother. 2006 Nov;50(11):3917-9. Epub 2006 Sep 11. [PubMed:16966400]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sterol 14-demethylase activity
Specific Function
Catalyzes C14-demethylation of lanosterol; it transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol.
Gene Name
CYP51A1
Uniprot ID
Q16850
Uniprot Name
Lanosterol 14-alpha demethylase
Molecular Weight
56805.26 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Fliri AF, Loging WT, Thadeio PF, Volkmann RA: Biological spectra analysis: Linking biological activity profiles to molecular structure. Proc Natl Acad Sci U S A. 2005 Jan 11;102(2):261-6. Epub 2004 Dec 29. [PubMed:15625110]
  4. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxygen binding
Specific Function
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name
CYP19A1
Uniprot ID
P11511
Uniprot Name
Aromatase
Molecular Weight
57882.48 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Current data supporting this enzyme inhibition is limited to one in vitro study.
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Zhang W, Ramamoorthy Y, Kilicarslan T, Nolte H, Tyndale RF, Sellers EM: Inhibition of cytochromes P450 by antifungal imidazole derivatives. Drug Metab Dispos. 2002 Mar;30(3):314-8. [PubMed:11854151]
  3. Sweeney BP, Bromilow J: Liver enzyme induction and inhibition: implications for anaesthesia. Anaesthesia. 2006 Feb;61(2):159-77. doi: 10.1111/j.1365-2044.2005.04462.x. [PubMed:16430569]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic ...
Gene Name
CYP2E1
Uniprot ID
P05181
Uniprot Name
Cytochrome P450 2E1
Molecular Weight
56848.42 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Zhang W, Ramamoorthy Y, Kilicarslan T, Nolte H, Tyndale RF, Sellers EM: Inhibition of cytochromes P450 by antifungal imidazole derivatives. Drug Metab Dispos. 2002 Mar;30(3):314-8. [PubMed:11854151]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Zhang W, Ramamoorthy Y, Kilicarslan T, Nolte H, Tyndale RF, Sellers EM: Inhibition of cytochromes P450 by antifungal imidazole derivatives. Drug Metab Dispos. 2002 Mar;30(3):314-8. [PubMed:11854151]

Drug created on June 13, 2005 07:24 / Updated on December 14, 2018 17:08