T3DB: Kojic acid

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (4)XML

Targets (4)

Record Information

Version

2.0

Creation Date

2010-05-21 16:18:59 UTC

Update Date

2014-12-24 20:26:31 UTC

Accession Number

T3D3769

Identification

Common Name

Kojic acid

Class

Small Molecule

Description

Kojic 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

MOL SDF PDB SMILES InChI

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 Formula

C₆H₆O₄

Average Molecular Mass

142.109 g/mol

Monoisotopic Mass

142.027 g/mol

CAS Registry Number

501-30-4

IUPAC Name

5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one

Traditional Name

kojic acid

SMILES

OCC1=CC(=O)C(O)=CO1

InChI Identifier

InChI=1S/C6H6O4/c7-2-4-1-5(8)6(9)3-10-4/h1,3,7,9H,2H2

InChI Key

InChIKey=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.

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Pyrans

Sub Class

Pyranones and derivatives

Direct Parent

Pyranones 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 Framework

Aromatic heteromonocyclic compounds

External Descriptors

primary alcohol (CHEBI:43572 )
pyranone (CHEBI:43572 )
enol (CHEBI:43572 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cytoplasm
Extracellular

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Not Available

Applications

Not Available

Biological Roles

Aspergillus metabolite

Chemical Roles

NF-kappaB inhibitor

Physical Properties

State

Solid

Appearance

Tan powder.

Experimental Properties

Property	Value
Melting Point	161°C
Boiling Point	Not Available
Solubility	Not Available
LogP	-0.64

Predicted Properties

Property	Value	Source
Water Solubility	92.3 g/L	ALOGPS
logP	-1	ALOGPS
logP	-0.5	ChemAxon
logS	-0.19	ALOGPS
pKa (Strongest Acidic)	9.3	ChemAxon
pKa (Strongest Basic)	-3.1	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	4	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	66.76 Å²	ChemAxon
Rotatable Bond Count	1	ChemAxon
Refractivity	35.27 m³·mol⁻¹	ChemAxon
Polarizability	12.63 Å³	ChemAxon
Number of Rings	1	ChemAxon
Bioavailability	1	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
GC-MS	GC-MS Spectrum - GC-MS (2 TMS)	splash10-00di-3950000000-d1e6f5b2e47ac5626c5f	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-05p6-9300000000-704def65872ec878b268	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-00ko-9500000000-8c8ed21581e5ce62d657	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - EI-B (Non-derivatized)	splash10-00dj-0972200000-d2e1134bffb7759fab36	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-00dj-1940000000-7a8f18adc19d5275d098	2017-09-12	View Spectrum
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-00di-3950000000-d1e6f5b2e47ac5626c5f	2017-09-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-03kc-6900000000-d96f98a42148a6e47233	2017-09-01	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positive	splash10-00di-9650000000-945de47e75f8ec9b9eaf	2017-10-06	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , negative	splash10-0006-0900000000-7497f496112e599fe169	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Linear Ion Trap , negative	splash10-001i-9200000000-79391fb0052779fa15a9	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Negative	splash10-0006-0900000000-7497f496112e599fe169	2021-09-20	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0006-0900000000-b4f5c76df606bee2639b	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0006-1900000000-8c591424fe1f23b4f463	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0a6r-9300000000-2f1a2b3413e8f032697f	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0006-0900000000-a3e3f8a5e8ce22a6cba3	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-01ox-2900000000-4f881cf1625489e94838	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-052f-9000000000-82a828b03c7d45e6515f	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-004l-1900000000-9f54abebd3fd9066985d	2021-09-24	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-00ov-9600000000-4e5e43090310b4854d93	2021-09-24	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0006-9100000000-20c19898fd61a4ca36ac	2021-09-24	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0006-0900000000-781e0069db86c3955b89	2021-09-24	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0006-9400000000-c6bf0fd6d0995684723a	2021-09-24	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-0006-9000000000-63243637491eb161d9df	2021-09-24	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-00kf-9400000000-15508d600420b309e528	2014-09-20	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 100 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 1000 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 200 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 300 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 400 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 500 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 600 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 700 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 800 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹H NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum
1D NMR	¹³C NMR Spectrum (1D, 900 MHz, D₂O, predicted)	Not Available	2021-09-25	View Spectrum

Toxicity Profile

Route of Exposure

Oral, dermal, inhalation, and parenteral (contaminated drugs). (3)

Mechanism of Toxicity

Kojic 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)

Metabolism

Kojic acid is absorbed by the gastrointestinal tract, enters the circulation, and is probably metabolized similar to hexoses. (1)

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

3, not classifiable as to its carcinogenicity to humans. (7)

Uses/Sources

Kojic 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 Level

Not Available

Health Effects

Animals 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)

Symptoms

Sensitive individuals may develop contact dermatitis. (1)

Treatment

Not Available

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

DB01759

HMDB ID

HMDB32923

PubChem Compound ID

3840

ChEMBL ID

Not Available

ChemSpider ID

3708

KEGG ID

C14516

UniProt ID

Not Available

OMIM ID

ChEBI ID

34805

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

KOJ

ACToR ID

Not Available

Wikipedia Link

Kojic_acid

References

Synthesis Reference

Not Available

MSDS

Link

General References

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 ]
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 ]
Peraica M, Domijan AM: Contamination of food with mycotoxins and human health. Arh Hig Rada Toksikol. 2001 Mar;52(1):23-35. [11370295 ]
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 ]
Yannai, Shmuel. (2004) Dictionary of food compounds with CD-ROM: Additives, flavors, and ingredients. Boca Raton: Chapman & Hall/CRC.
Wikipedia. Kojic acid. Last Updated 14 May 2010. [Link]
International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]

Gene Regulation

Up-Regulated Genes

Gene	Gene Symbol	Gene ID	Interaction	Chromosome	Details

Down-Regulated Genes

Gene	Gene Symbol	Gene ID	Interaction	Chromosome	Details

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

Type	Value	Assay Type	Assay Source
IC50	7.4 uM	Not Available	BindingDB 50031467
IC50	16.67 uM	Not Available	BindingDB 50031467
IC50	16.7 uM	Not Available	BindingDB 50031467
IC50	22.94 uM	Not Available	BindingDB 50031467
IC50	66.55 uM	Not Available	BindingDB 50031467
IC50	125 uM	Not Available	BindingDB 50031467
IC50	133.4 uM	Not Available	BindingDB 50031467
IC50	280 uM	Not Available	BindingDB 50031467

References

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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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

Type	Value	Assay Type	Assay Source
IC50	2 uM	Not Available	BindingDB 50031467

References

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 ]
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

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

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 ]

Kojic acid (T3D3769)

Structure for T3D3769: Kojic acid

Targets

Binding/Activity Constants

References

Binding/Activity Constants

References

References

References