Aflatoxin M1 (T3D3666)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (2)XML
Targets (2)
Record Information
Version2.0
Creation Date2010-04-13 22:40:51 UTC
Update Date2014-12-24 20:26:19 UTC
Accession NumberT3D3666
Identification
Common NameAflatoxin M1
ClassSmall Molecule
DescriptionAflatoxin M1 is found in milk and milk products. Minor mycotoxin of Aspergillus flavus, also found in the milk of cows and sheep fed toxic meal. Metab. of Aflatoxin B1 JHZ87-P [CCD].Aflatoxins are naturally occurring mycotoxins that are produced by many species of Aspergillus, a fungus, most notably Aspergillus flavus and Aspergillus parasiticus. Aflatoxins are toxic and among the most carcinogenic substances known. Aflatoxin M1 is a metabolite of aflatoxin B1 in humans and animals. (Wikipedia) Aflatoxin m1 belongs to the family of Difurocoumarocyclopentenone Series. These are polycyclic aromatic compounds containing a cyclopenten-2-one ring fused to the coumarin moiety of the difurocoumarin skeleton. Difurocoumarocyclopentenones are a subgroup of the aflatoxins and related compounds.
Compound Type
  • Ester
  • Ether
  • Food Toxin
  • Fungal Toxin
  • Metabolite
  • Mycotoxin
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
Synonym
4-Hydroxyaflatoxin B1
Aflatoxin m1
Chemical FormulaC17H12O7
Average Molecular Mass328.273 g/mol
Monoisotopic Mass328.058 g/mol
CAS Registry Number6795-23-9
IUPAC Name3-hydroxy-11-methoxy-6,8,19-trioxapentacyclo[10.7.0.0²,⁹.0³,⁷.0¹³,¹⁷]nonadeca-1(12),2(9),4,10,13(17)-pentaene-16,18-dione
Traditional Nameaflatoxin M1
SMILESCOC1=CC2=C(C3=C1C1=C(C(=O)CC1)C(=O)O3)C1(O)C=COC1O2
InChI IdentifierInChI=1/C17H12O7/c1-21-9-6-10-13(17(20)4-5-22-16(17)23-10)14-12(9)7-2-3-8(18)11(7)15(19)24-14/h4-6,16,20H,2-3H2,1H3
InChI KeyInChIKey=MJBWDEQAUQTVKK-UHFFFAOYNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as difurocoumarocyclopentenones. These are polycyclic aromatic compounds containing a cyclopenten-2-one ring fused to the coumarin moiety of the difurocoumarin skeleton.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassCoumarins and derivatives
Sub ClassFuranocoumarins
Direct ParentDifurocoumarocyclopentenones
Alternative Parents
Substituents
  • Difurocoumarocyclopentenone
  • Benzopyran
  • 1-benzopyran
  • Coumaran
  • Anisole
  • Aryl alkyl ketone
  • Aryl ketone
  • Alkyl aryl ether
  • Pyranone
  • Pyran
  • Benzenoid
  • Tertiary alcohol
  • Dihydrofuran
  • Heteroaromatic compound
  • Lactone
  • Ketone
  • Acetal
  • Oxacycle
  • Ether
  • Organoheterocyclic compound
  • Organooxygen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organic oxygen compound
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceColorless to pale yellow crystals.
Experimental Properties
PropertyValue
Melting Point299°C
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.99 g/LALOGPS
logP1.21ALOGPS
logP0.93ChemAxon
logS-2.5ALOGPS
pKa (Strongest Acidic)11.42ChemAxon
pKa (Strongest Basic)-4.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area91.29 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity79.67 m³·mol⁻¹ChemAxon
Polarizability31.02 ųChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-004i-0019000000-ed1a7dfa6d8bdd4f1c482016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004i-0039000000-2cd79d60556438462dc22016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-03xs-2390000000-b22ffb9577209213cde42016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0029000000-927508d8713045699f272016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004i-0039000000-f1846ea7b90515ff572e2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-03fu-2290000000-0ca55a29e3b2c2b177302016-08-03View Spectrum
Toxicity Profile
Route of ExposureOral, dermal, inhalation, and parenteral (contaminated drugs). (4)
Mechanism of ToxicityAflatoxins produce singlet oxygen upon their exposure to UV (365-nm) light. Singlet oxygen in turn activates them to mutagens and DNA binding species. Aflatoxin M1 is P450 activated to its epoxide. Aflatoxin metabolites can intercalate into DNA and alkylate the bases through their epoxide moiety, binding particularity to N7-guanine bases. In addition to randomly mutating DNA, this is thought to cause mutations in the p53 gene, an important gene in preventing cell cycle progression when there are DNA mutations, or signaling apoptosis. (8, 1, 3)
MetabolismAflatoxin M1 is P450 activated to its epoxide and detoxified by glutathione S transferase. [Pubchem] (3)
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)2B, possibly carcinogenic to humans. (11)
Uses/SourcesThe native habitat of Aspergillus is in soil, decaying vegetation, hay, and grains undergoing microbiological deterioration and it invades all types of organic substrates whenever conditions are favorable for its growth. Crops which are frequently affected include cereals (maize, sorghum, pearl millet, rice, wheat), oilseeds (peanut, soybean, sunflower, cotton), spices (chile peppers, black pepper, coriander, turmeric, ginger), and tree nuts (almond, pistachio, walnut, coconut, brazil nut). The toxin can also be found in the milk of animals which are fed contaminated feed. Thus, aflatoxins are usually encountered in thecontext of chronic exposure, via food intake or secondary to the handling of foodstuffs. (10)
Minimum Risk LevelNot Available
Health EffectsThe main target organ in mammals is the liver so aflatoxicosis is primarily a hepatic disease. Protracted exposure to aflatoxins may cause liver damage and necrosis, cholestasis, and hepatomas. Moreover, protracted exposure to aflatoxins has been associated with hepatocellular carcinoma, acute hepatitis, Reye's syndrome, bile duct cell proliferation, periportal fibrosis, hemorrhages, mucous membrane jaundice, fatty liver changes, cirrhosis in malnourished children, and kwashiorkor. However, aflatoxins accumulate in the presence of liver disease, and the association with hepatic cancer is confounded by the occurrence of hepatitis-B. Thus, it is not clear in these various instances whether aflatoxin is a primary cause of the disease, is an innocent bystander which accumulates secondary to the disease process, or is a contributing cause in conjunction with other factors. It is also mutagenic and teratogenic. Inhaled aflatoxins may produce pulmonary adenomatosis. Aflatoxins modify the immune system by affecting antibody formation, complement, cell-mediated immunity, and phagocytosis. (5, 10)
SymptomsA broad range of symptoms can be found depending upon dosage, including, vomiting, abdominal pain, hemorrhage, and pulmonary edema. (9)
TreatmentAdministration of phonobarbital enhances hepatic transformation activities and also protects against AFB-induced toxicity, carcinogenicity and DNA binding in vivo. In cases of ingestion, feeding large quantities of an adsorbent such as activated charcoal may be used. Antioxidants such as ellagic acid and inducers of some cytochromes P450, such as indole-3-carbinol, may give a protective effect. (5, 9)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB30479
PubChem Compound ID15558498
ChEMBL IDNot Available
ChemSpider ID21169428
KEGG IDC16756
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkAflatoxin
References
Synthesis ReferenceNot Available
MSDST3D3666.pdf
General References
  1. Stark AA, Liberman DF: Synergism between aflatoxins in covalent binding to DNA and in mutagenesis in the photoactivation system. Mutat Res. 1991 Mar;247(1):77-86. [1900569 ]
  2. Guengerich FP, Johnson WW, Ueng YF, Yamazaki H, Shimada T: Involvement of cytochrome P450, glutathione S-transferase, and epoxide hydrolase in the metabolism of aflatoxin B1 and relevance to risk of human liver cancer. Environ Health Perspect. 1996 May;104 Suppl 3:557-62. [8781383 ]
  3. Eaton DL, Gallagher EP: Mechanisms of aflatoxin carcinogenesis. Annu Rev Pharmacol Toxicol. 1994;34:135-72. [8042848 ]
  4. Peraica M, Domijan AM: Contamination of food with mycotoxins and human health. Arh Hig Rada Toksikol. 2001 Mar;52(1):23-35. [11370295 ]
  5. Grond S, Sablotzki A: Clinical pharmacology of tramadol. Clin Pharmacokinet. 2004;43(13):879-923. [15509185 ]
  6. Rumack BH POISINDEX(R) Information System Micromedex, Inc., Englewood, CO, 2010; CCIS Volume 143, edition expires Feb, 2010. Hall AH & Rumack BH (Eds): TOMES(R) Information System Micromedex, Inc., Englewood, CO, 2010; CCIS Volume 143, edition expires Feb, 2010.
  7. Yannai, Shmuel. (2004) Dictionary of food compounds with CD-ROM: Additives, flavors, and ingredients. Boca Raton: Chapman & Hall/CRC.
  8. International Agency for Research on Cancer (IARC) - Summaries & Evaluations AFLATOXINS [Link]
  9. Aflatoxins: essential data [Link]
  10. Wikipedia. Aflatoxin. Last Updated 3 May 2010. [Link]
  11. 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 GenesNot Available

Targets

1. DNA
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Stark AA, Liberman DF: Synergism between aflatoxins in covalent binding to DNA and in mutagenesis in the photoactivation system. Mutat Res. 1991 Mar;247(1):77-86. [1900569 ]
  2. Eaton DL, Gallagher EP: Mechanisms of aflatoxin carcinogenesis. Annu Rev Pharmacol Toxicol. 1994;34:135-72. [8042848 ]
  3. International Agency for Research on Cancer (IARC) - Summaries & Evaluations AFLATOXINS [Link]
Target Details
2. Alpha-S1-casein
General Function:
Transporter activity
Specific Function:
Important role in the capacity of milk to transport calcium phosphate.Casoxin D acts as opioid antagonist and has vasorelaxing activity mediated by bradykinin B1 receptors.
Gene Name:
CSN1S1
Uniprot ID:
P47710
Molecular Weight:
21671.33 Da
References
  1. Brackett RE, Marth EH: Association of aflatoxin M1 with casein. Z Lebensm Unters Forsch. 1982;174(6):439-41. [6812308 ]