Tioconazole (T3D2956)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (2)XML
Targets (2)
Record Information
Version2.0
Creation Date2009-07-21 20:28:09 UTC
Update Date2014-12-24 20:25:54 UTC
Accession NumberT3D2956
Identification
Common NameTioconazole
ClassSmall Molecule
DescriptionTioconazole 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.
Compound Type
  • 14-alpha Demethylase Inhibitor
  • Amine
  • Antifungal Agent
  • Drug
  • Ether
  • Metabolite
  • Organic Compound
  • Organochloride
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
GyneCure
Monistat 1
Tioconazol
Tioconazolum
Trosyd
Trosyl
Vagistat-1
Chemical FormulaC16H13Cl3N2OS
Average Molecular Mass387.711 g/mol
Monoisotopic Mass385.981 g/mol
CAS Registry Number65899-73-2
IUPAC Name1-{2-[(2-chlorothiophen-3-yl)methoxy]-2-(2,4-dichlorophenyl)ethyl}-1H-imidazole
Traditional Nametioconazole
SMILESClC1=C(COC(CN2C=CN=C2)C2=C(Cl)C=C(Cl)C=C2)C=CS1
InChI IdentifierInChI=1/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
InChI KeyInChIKey=QXHHHPZILQDDPS-UHFFFAOYNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as benzylethers. These are aromatic ethers with the general formula ROCR' (R = alkyl, aryl; R'=benzene).
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzylethers
Direct ParentBenzylethers
Alternative Parents
Substituents
  • Benzylether
  • 1,3-dichlorobenzene
  • Chlorobenzene
  • Halobenzene
  • Aryl chloride
  • Aryl halide
  • N-substituted imidazole
  • Azole
  • Heteroaromatic compound
  • Thiophene
  • Imidazole
  • Azacycle
  • Dialkyl ether
  • Organoheterocyclic compound
  • Ether
  • Organopnictogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
Solubility1.65e-02 g/L
LogP4.4
Predicted Properties
PropertyValueSource
Water Solubility0.016 g/LALOGPS
logP4.86ALOGPS
logP5.3ChemAxon
logS-4.4ALOGPS
pKa (Strongest Basic)6.77ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area27.05 ŲChemAxon
Rotatable Bond Count6ChemAxon
Refractivity94.53 m³·mol⁻¹ChemAxon
Polarizability36.84 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-001i-9322000000-f6f11c3dd1abefdb54722017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-000i-0009000000-2827a77fbda828e7453e2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-000i-0009000000-27b855fca59ed08acb852017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-001i-0903000000-30ef91f27453208dd5842017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-001i-0900000000-2ed7f788cac071d871e42017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-001i-0900000000-94a2a2533441e31796632017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-IT , positivesplash10-001i-0900000000-fa59d0317db7f93d6c2a2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0019-1619000000-7bfbe2de2c4aa4e6cd392017-09-14View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0019000000-9710e360ac903a19e7612016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00kr-4059000000-11184eccc1c4190d1d562016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-014i-9220000000-92260c4a2b938613c3912016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001i-2009000000-694e0b1bbedf8c9a518a2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-014i-9002000000-892ee7d55153e17c3fb52016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-014l-9110000000-a6e3b216a6c36e5201db2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0009000000-46e7ef27c173cdeac9262021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-000i-0009000000-55ff8b5cd7b6cb6c4a942021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-014i-9620000000-6425beede3614c6e9d8f2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-001r-2089000000-ebf536df5e672f10ce982021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001i-9420000000-122db257637508515ef42021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00lr-9010000000-fb107803b0fd9576864e2021-10-11View Spectrum
Toxicity Profile
Route of ExposureSystemic absorption following a single intravaginal application of tioconazole in nonpregnant patients is negligible.
Mechanism of ToxicityTioconazole 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.
MetabolismOrally administered tioconazole is extensively metabolized. The major metabolites are glucuronide conjugates.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the local treatment of vulvovaginal candidiasis (moniliasis).
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSymptoms of overdose include erythema, stinging, blistering, peeling, edema, pruritus, urticaria, burning, and general irritation of the skin, and cramps.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01007
HMDB IDHMDB15142
PubChem Compound ID5482
ChEMBL IDCHEMBL1200438
ChemSpider ID5282
KEGG IDC08082
UniProt IDNot Available
OMIM ID
ChEBI ID774389
BioCyc IDNot Available
CTD IDNot Available
Stitch IDTioconazole
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkTioconazole
References
Synthesis ReferenceNot Available
MSDST3D2956.pdf
General References
  1. Drugs.com [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Lanosterol 14-alpha demethylase
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
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. [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. [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. [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. [10592235 ]
Target Details
2. Steroid 17-alpha-hydroxylase/17,20 lyase
General Function:
Steroid 17-alpha-monooxygenase activity
Specific Function:
Conversion of pregnenolone and progesterone to their 17-alpha-hydroxylated products and subsequently to dehydroepiandrosterone (DHEA) and androstenedione. Catalyzes both the 17-alpha-hydroxylation and the 17,20-lyase reaction. Involved in sexual development during fetal life and at puberty.
Gene Name:
CYP17A1
Uniprot ID:
P05093
Molecular Weight:
57369.995 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.505 uMNot AvailableBindingDB 50370218
References
  1. Clement OO, Freeman CM, Hartmann RW, Handratta VD, Vasaitis TS, Brodie AM, Njar VC: Three dimensional pharmacophore modeling of human CYP17 inhibitors. Potential agents for prostate cancer therapy. J Med Chem. 2003 Jun 5;46(12):2345-51. [12773039 ]