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Kojic acid (T3D3769)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (4)XML
Targets (4)
Record Information
Version2.0
Creation Date2010-05-21 16:18:59 UTC
Update Date2014-12-24 20:26:31 UTC
Accession NumberT3D3769
Identification
Common NameKojic acid
ClassSmall Molecule
DescriptionKojic acid is a synthetic intermediate for production of food additives. Kojic acid has been shown to exhibit anti-neoplastic function (4).
Compound Type
  • Ester
  • Food Toxin
  • Fungal Toxin
  • Industrial/Workplace Toxin
  • Metabolite
  • Mycotoxin
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
2-(Hydroxymethyl)-5-hydroxy-4H-pyran-4-one
2-Hydroxymethyl-5-hydroxy-gamma-pyrone
5-Hydroxy-2-(hydroxymethyl)-4-pyrone
5-Hydroxy-2-(hydroxymethyl)-4H-Pyran-4-one
5-Hydroxy-2-(hydroxymethyl)pyran-4-one
5-Hydroxy-2-hydroxymethyl-4-pyrone
5-Hydroxy-2-hydroxymethyl-4H-4-pyranone
Acido kojico
KOJ
Kojate
Pyran-4-one, 5-hydroxy-2-(hydroxymethyl)
Chemical FormulaC6H6O4
Average Molecular Mass142.109 g/mol
Monoisotopic Mass142.027 g/mol
CAS Registry Number501-30-4
IUPAC Name5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one
Traditional Namekojic acid
SMILESOCC1=CC(=O)C(O)=CO1
InChI IdentifierInChI=1S/C6H6O4/c7-2-4-1-5(8)6(9)3-10-4/h1,3,7,9H,2H2
InChI KeyInChIKey=BEJNERDRQOWKJM-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as pyranones and derivatives. Pyranones and derivatives are compounds containing a pyran ring which bears a ketone.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassPyrans
Sub ClassPyranones and derivatives
Direct ParentPyranones and derivatives
Alternative Parents
Substituents
  • Pyranone
  • Heteroaromatic compound
  • Cyclic ketone
  • Oxacycle
  • Organic oxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Aromatic alcohol
  • Primary alcohol
  • Organooxygen compound
  • Alcohol
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceTan powder.
Experimental Properties
PropertyValue
Melting Point161°C
Boiling PointNot Available
SolubilityNot Available
LogP-0.64
Predicted Properties
PropertyValueSource
Water Solubility92.3 g/LALOGPS
logP-1ALOGPS
logP-0.5ChemAxon
logS-0.19ALOGPS
pKa (Strongest Acidic)9.3ChemAxon
pKa (Strongest Basic)-3.1ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area66.76 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity35.27 m³·mol⁻¹ChemAxon
Polarizability12.63 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-MS (2 TMS)splash10-00di-3950000000-d1e6f5b2e47ac5626c5fView in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-05p6-9300000000-704def65872ec878b268View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-00ko-9500000000-8c8ed21581e5ce62d657View in MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-00dj-0972200000-d2e1134bffb7759fab36View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-00dj-1940000000-7a8f18adc19d5275d098View in MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-00di-3950000000-d1e6f5b2e47ac5626c5fView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-03kc-6900000000-d96f98a42148a6e47233View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-00di-9650000000-945de47e75f8ec9b9eafView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-0006-0900000000-7497f496112e599fe169View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , negativesplash10-001i-9200000000-79391fb0052779fa15a9View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0006-0900000000-b4f5c76df606bee2639bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0006-1900000000-8c591424fe1f23b4f463View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a6r-9300000000-2f1a2b3413e8f032697fView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-0900000000-a3e3f8a5e8ce22a6cba3View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-01ox-2900000000-4f881cf1625489e94838View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-052f-9000000000-82a828b03c7d45e6515fView in MoNA
MSMass Spectrum (Electron Ionization)splash10-00kf-9400000000-15508d600420b309e528View in MoNA
Toxicity Profile
Route of ExposureOral, dermal, inhalation, and parenteral (contaminated drugs). (3)
Mechanism of ToxicityKojic acid acts as a competitive and reversible inhibitor of animal and plant polyphenol oxidases (tyrosinases), xanthine oxidase, and D- and some L-amino acid oxidases. Inhibition of tyrosinases prevents melanosis, while inhibition of the oxidases prevents metabolism of certain amino acids. Kojic acid also reversibly affects thyroid function by inhibiting iodine uptake, leading to decreases in thyroid hormones T3 and T4 and increases in thyroid-stimulating hormone (TSH). Increased TSH from pituitary gland in turn stimulates thyroid hyperplasia. (1, 2)
MetabolismKojic acid is absorbed by the gastrointestinal tract, enters the circulation, and is probably metabolized similar to hexoses. (1)
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)3, not classifiable as to its carcinogenicity to humans. (7)
Uses/SourcesKojic acid is a chelation agent and mycotoxin produced by several species of Aspergillus, Acetobacter, and Penicillium fungi, especially Aspergillus oryzae, which has the Japanese common name koji. Kojic acid is a by-product in the fermentation process of malting rice, and is used in the manufacturing of numerous foods, including miso, soy sauce, and sake. Kojic acid is a mild inhibitor of the formation of pigment in plant and animal tissues, and is used in food and cosmetics to preserve or change colors of substances, such as in skin-lightening or bleaching formulas. It is also used as a food additive for preventing enzymatic browning and in seafood to preserve pink and red colors. Kojic acid also has antibacterial and antifungal properties and is used in skin diseases like melasma. (6, 1)
Minimum Risk LevelNot Available
Health EffectsAnimals studies have shown that kojic acid increases the occurrence of thyroid cancer and thyroid adenomas, though it is not known whether this is also true in humans. (1)
SymptomsSensitive individuals may develop contact dermatitis. (1)
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01759
HMDB IDHMDB32923
PubChem Compound ID3840
ChEMBL IDNot Available
ChemSpider ID3708
KEGG IDC14516
UniProt IDNot Available
OMIM ID
ChEBI ID34805
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDKOJ
ACToR IDNot Available
Wikipedia LinkKojic_acid
References
Synthesis ReferenceNot Available
MSDSLink
General References
  1. Burdock GA, Soni MG, Carabin IG: Evaluation of health aspects of kojic acid in food. Regul Toxicol Pharmacol. 2001 Feb;33(1):80-101. [11259181 ]
  2. Noh JM, Kwak SY, Seo HS, Seo JH, Kim BG, Lee YS: Kojic acid-amino acid conjugates as tyrosinase inhibitors. Bioorg Med Chem Lett. 2009 Oct 1;19(19):5586-9. doi: 10.1016/j.bmcl.2009.08.041. Epub 2009 Aug 14. [19700313 ]
  3. Peraica M, Domijan AM: Contamination of food with mycotoxins and human health. Arh Hig Rada Toksikol. 2001 Mar;52(1):23-35. [11370295 ]
  4. Novotny L, Rauko P, Abdel-Hamid M, Vachalkova A: Kojic acid--a new leading molecule for a preparation of compounds with an anti-neoplastic potential. Neoplasma. 1999;46(2):89-92. [10466431 ]
  5. Yannai, Shmuel. (2004) Dictionary of food compounds with CD-ROM: Additives, flavors, and ingredients. Boca Raton: Chapman & Hall/CRC.
  6. Wikipedia. Kojic acid. Last Updated 14 May 2010. [Link]
  7. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

Target Details
1. Tyrosinase
General Function:
Protein homodimerization activity
Specific Function:
This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds. Catalyzes the rate-limiting conversions of tyrosine to DOPA, DOPA to DOPA-quinone and possibly 5,6-dihydroxyindole to indole-5,6 quinone.
Gene Name:
TYR
Uniprot ID:
P14679
Molecular Weight:
60392.69 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC507.4 uMNot AvailableBindingDB 50031467
IC5016.67 uMNot AvailableBindingDB 50031467
IC5016.7 uMNot AvailableBindingDB 50031467
IC5022.94 uMNot AvailableBindingDB 50031467
IC5066.55 uMNot AvailableBindingDB 50031467
IC50125 uMNot AvailableBindingDB 50031467
IC50133.4 uMNot AvailableBindingDB 50031467
IC50280 uMNot AvailableBindingDB 50031467
References
  1. Burdock GA, Soni MG, Carabin IG: Evaluation of health aspects of kojic acid in food. Regul Toxicol Pharmacol. 2001 Feb;33(1):80-101. [11259181 ]
  2. Noh JM, Kwak SY, Seo HS, Seo JH, Kim BG, Lee YS: Kojic acid-amino acid conjugates as tyrosinase inhibitors. Bioorg Med Chem Lett. 2009 Oct 1;19(19):5586-9. doi: 10.1016/j.bmcl.2009.08.041. Epub 2009 Aug 14. [19700313 ]
  3. Tajima R, Oozeki H, Muraoka S, Tanaka S, Motegi Y, Nihei H, Yamada Y, Masuoka N, Nihei K: Synthesis and evaluation of bibenzyl glycosides as potent tyrosinase inhibitors. Eur J Med Chem. 2011 Apr;46(4):1374-81. doi: 10.1016/j.ejmech.2011.01.065. Epub 2011 Feb 3. [21334791 ]
  4. Casanola-Martin GM, Khan MT, Marrero-Ponce Y, Ather A, Sultankhodzhaev MN, Torrens F: New tyrosinase inhibitors selected by atomic linear indices-based classification models. Bioorg Med Chem Lett. 2006 Jan 15;16(2):324-30. Epub 2005 Nov 3. [16275084 ]
  5. Khan KM, Saify ZS, Khan MT, Butt N, Maharvi GM, Perveen S, Ambreen N, Choudhary MI, Atta-Ur-Rahman, Supuran CT: Tyrosinase inhibition: conformational analysis based studies on molecular dynamics calculations of bipiperidine based inhibitors. J Enzyme Inhib Med Chem. 2005 Aug;20(4):401-7. [16206837 ]
  6. Kim H, Choi J, Cho JK, Kim SY, Lee YS: Solid-phase synthesis of kojic acid-tripeptides and their tyrosinase inhibitory activity, storage stability, and toxicity. Bioorg Med Chem Lett. 2004 Jun 7;14(11):2843-6. [15125944 ]
  7. Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]
  8. Lee KH, Ab Aziz FH, Syahida A, Abas F, Shaari K, Israf DA, Lajis NH: Synthesis and biological evaluation of curcumin-like diarylpentanoid analogues for anti-inflammatory, antioxidant and anti-tyrosinase activities. Eur J Med Chem. 2009 Aug;44(8):3195-200. doi: 10.1016/j.ejmech.2009.03.020. Epub 2009 Mar 26. [19359068 ]
  9. Su CR, Kuo PC, Wang ML, Liou MJ, Damu AG, Wu TS: Acetophenone derivatives from Acronychia pedunculata. J Nat Prod. 2003 Jul;66(7):990-3. [12880321 ]
  10. Wu TS, Hsu MY, Kuo PC, Sreenivasulu B, Damu AG, Su CR, Li CY, Chang HC: Constituents from the leaves of Phellodendron amurense var. wilsonii and their bioactivity. J Nat Prod. 2003 Sep;66(9):1207-11. [14510598 ]
  11. Likhitwitayawuid K, Sornsute A, Sritularak B, Ploypradith P: Chemical transformations of oxyresveratrol (trans-2,4,3',5'-tetrahydroxystilbene) into a potent tyrosinase inhibitor and a strong cytotoxic agent. Bioorg Med Chem Lett. 2006 Nov 1;16(21):5650-3. Epub 2006 Aug 17. [16919455 ]
  12. Nihei Ki, Kubo I: Identification of oxidation product of arbutin in mushroom tyrosinase assay system. Bioorg Med Chem Lett. 2003 Jul 21;13(14):2409-12. [12824045 ]
Target Details
2. D-amino-acid oxidase
General Function:
Receptor binding
Specific Function:
Regulates the level of the neuromodulator D-serine in the brain. Has high activity towards D-DOPA and contributes to dopamine synthesis. Could act as a detoxifying agent which removes D-amino acids accumulated during aging. Acts on a variety of D-amino acids with a preference for those having small hydrophobic side chains followed by those bearing polar, aromatic, and basic groups. Does not act on acidic amino acids.
Gene Name:
DAO
Uniprot ID:
P14920
Molecular Weight:
39473.75 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC502 uMNot AvailableBindingDB 50031467
References
  1. Burdock GA, Soni MG, Carabin IG: Evaluation of health aspects of kojic acid in food. Regul Toxicol Pharmacol. 2001 Feb;33(1):80-101. [11259181 ]
  2. Raje M, Hin N, Duvall B, Ferraris DV, Berry JF, Thomas AG, Alt J, Rojas C, Slusher BS, Tsukamoto T: Synthesis of kojic acid derivatives as secondary binding site probes of D-amino acid oxidase. Bioorg Med Chem Lett. 2013 Jul 1;23(13):3910-3. doi: 10.1016/j.bmcl.2013.04.062. Epub 2013 May 1. [23683589 ]
Target Details
3. L-amino-acid oxidase
General Function:
L-amino-acid oxidase activity
Specific Function:
Lysosomal L-amino-acid oxidase with highest specific activity with phenylalanine. May play a role in lysosomal antigen processing and presentation (By similarity).
Gene Name:
IL4I1
Uniprot ID:
Q96RQ9
Molecular Weight:
62880.52 Da
References
  1. Burdock GA, Soni MG, Carabin IG: Evaluation of health aspects of kojic acid in food. Regul Toxicol Pharmacol. 2001 Feb;33(1):80-101. [11259181 ]
Target Details
4. Xanthine dehydrogenase/oxidase
General Function:
Xanthine oxidase activity
Specific Function:
Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Has also low oxidase activity towards aldehydes (in vitro).
Gene Name:
XDH
Uniprot ID:
P47989
Molecular Weight:
146422.99 Da
References
  1. Burdock GA, Soni MG, Carabin IG: Evaluation of health aspects of kojic acid in food. Regul Toxicol Pharmacol. 2001 Feb;33(1):80-101. [11259181 ]