| Record Information |
|---|
| Version | 2.0 |
|---|
| Creation Date | 2010-04-15 17:21:01 UTC |
|---|
| Update Date | 2014-12-24 20:26:20 UTC |
|---|
| Accession Number | T3D3672 |
|---|
| Identification |
|---|
| Common Name | Aflatoxin M2 |
|---|
| Class | Small Molecule |
|---|
| Description | Trace mycotoxin of Aspergillus flavus [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 M2 is a metabolite of aflatoxin B2 in milk of cattle fed on contaminated foods. (Wikipedia)
Aflatoxin M2 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
- Furocoumarin
- Metabolite
- Mycotoxin
- Natural Compound
- Organic Compound
|
|---|
| Chemical Structure | |
|---|
| Synonyms | | Synonym | | 4-Hydroxyaflatoxin B2 | | Aflatoxin m2 |
|
|---|
| Chemical Formula | C17H14O7 |
|---|
| Average Molecular Mass | 330.289 g/mol |
|---|
| Monoisotopic Mass | 330.074 g/mol |
|---|
| CAS Registry Number | 6885-57-0 |
|---|
| IUPAC Name | 3-hydroxy-11-methoxy-6,8,19-trioxapentacyclo[10.7.0.0²,⁹.0³,⁷.0¹³,¹⁷]nonadeca-1(12),2(9),10,13(17)-tetraene-16,18-dione |
|---|
| Traditional Name | aflatoxin M2 |
|---|
| SMILES | COC1=CC2=C(C3=C1C1=C(C(=O)CC1)C(=O)O3)C1(O)CCOC1O2 |
|---|
| InChI Identifier | InChI=1/C17H14O7/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/h6,16,20H,2-5H2,1H3 |
|---|
| InChI Key | InChIKey=OQLKWHFMUPJCJY-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. |
|---|
| Kingdom | Organic compounds |
|---|
| Super Class | Phenylpropanoids and polyketides |
|---|
| Class | Coumarins and derivatives |
|---|
| Sub Class | Furanocoumarins |
|---|
| Direct Parent | Difurocoumarocyclopentenones |
|---|
| Alternative Parents | |
|---|
| Substituents | - Difurocoumarocyclopentenone
- Difurocoumarin
- Benzopyran
- 1-benzopyran
- Coumaran
- Anisole
- Aryl ketone
- Aryl alkyl ketone
- Alkyl aryl ether
- Pyranone
- Benzenoid
- Pyran
- Heteroaromatic compound
- Tetrahydrofuran
- Tertiary alcohol
- Ketone
- Lactone
- Oxacycle
- Ether
- Acetal
- Organoheterocyclic compound
- Hydrocarbon derivative
- Organic oxide
- Organic oxygen compound
- Alcohol
- Organooxygen compound
- Aromatic heteropolycyclic compound
|
|---|
| Molecular Framework | Aromatic heteropolycyclic compounds |
|---|
| External Descriptors | Not Available |
|---|
| Biological Properties |
|---|
| Status | Detected and Not Quantified |
|---|
| Origin | Exogenous |
|---|
| Cellular Locations | |
|---|
| Biofluid Locations | Not Available |
|---|
| Tissue Locations | Not Available |
|---|
| Pathways | Not Available |
|---|
| Applications | Not Available |
|---|
| Biological Roles | Not Available |
|---|
| Chemical Roles | Not Available |
|---|
| Physical Properties |
|---|
| State | Solid |
|---|
| Appearance | Colorless to pale yellow crystals. |
|---|
| Experimental Properties | | Property | Value |
|---|
| Melting Point | 293°C | | Boiling Point | Not Available | | Solubility | Not Available | | LogP | Not Available |
|
|---|
| Predicted Properties | |
|---|
| Spectra |
|---|
| Spectra | | Spectrum Type | Description | Splash Key | Deposition Date | View |
|---|
| Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Positive | splash10-001i-0019000000-b1f144b2dce43edf2e65 | 2016-08-03 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Positive | splash10-01q9-0149000000-8f689b4babef5e140252 | 2016-08-03 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Positive | splash10-016s-1290000000-f913bc79ae59711dbe68 | 2016-08-03 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 10V, Negative | splash10-004i-0029000000-65dcb1efdd37df103d7f | 2016-08-03 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 20V, Negative | splash10-004i-1059000000-a3901977e0e73261a3c2 | 2016-08-03 | View Spectrum | | Predicted LC-MS/MS | Predicted LC-MS/MS Spectrum - 40V, Negative | splash10-01tc-3190000000-e5db2af5579765c8baca | 2016-08-03 | View Spectrum |
|
|---|
| Toxicity Profile |
|---|
| Route of Exposure | Oral, dermal, inhalation, and parenteral (contaminated drugs). (4) |
|---|
| Mechanism of Toxicity | Aflatoxins produce singlet oxygen upon their exposure to UV (365-nm) light. Singlet oxygen in turn activates them to mutagens and DNA binding species. 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. (11, 1, 2) The mechanism of action many furocoumarins is based on their ability to form photoadducts with DNA and other cellular components such as RNA, proteins, and several proteins found in the membrane such as phospholipases A2 and C, Ca-dependent and cAMPdependent protein-kinase and epidermal growth factor. Furocoumarins intercalate between base pairs of DNA and after ultraviolet-A irradiation, giving cycloadducts. (14) |
|---|
| Metabolism | Aflatoxins are metabolized in the liver by the cytochrome P-450-dependent polysubstrate mono-oxygenase system to less toxic metabolites. The main reactions in aflatoxin metabolism are hydroxylation, oxidation, and demethylation. (3) |
|---|
| Toxicity Values | Not Available |
|---|
| Lethal Dose | Not Available |
|---|
| Carcinogenicity (IARC Classification) | Not directly listed by IARC. IARC evaluated aflatoxins other than aflatoxin M2 and concluded that aflatoxins are carcinogenic to humans (Group 1). (15) |
|---|
| Uses/Sources | The 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. (13) |
|---|
| Minimum Risk Level | Not Available |
|---|
| Health Effects | The 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, 13) The furocoumarin 8-methoxypsoralen is carcinogenic to humans, and possibly 5-methoxypsoralen as well (15). There is some evidence from mouse studies that other furocoumarins are carcinogenic when combined with exposure to UVA radiation (6). The SKLM regards the additional risk of skin cancer arising from the consumption of typical quantities of furocoumarin-containing foods, which remain significantly below the range of phototoxic doses, as insignificant. However, the consumption of phototoxic quantities cannot be ruled out for certain foods, particularly celery and parsnips, that may lead to significant increases in furocoumarin concentrations, depending on the storage, processing and production conditions. (16) Furocoumarin photochemotherapy is known to induce a number of side-effects including erythema, edema, hyperpigmentation, and premature aging of skin. All photobiological effects of furocoumarins result from their photochemical reactions. Because many dietary or water soluble furocoumarins are strong inhibitors of cytochrome P450s, they will also cause adverse drug reactions when taken with other drugs. Limited evidence of carcinogenic effect. (14) |
|---|
| Symptoms | A broad range of symptoms can be found depending upon dosage, including, vomiting, abdominal pain, hemorrhage, and pulmonary edema. (12) |
|---|
| Treatment | Administration 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, 12) |
|---|
| Normal Concentrations |
|---|
| Not Available |
|---|
| Abnormal Concentrations |
|---|
| Not Available |
|---|
| External Links |
|---|
| DrugBank ID | Not Available |
|---|
| HMDB ID | HMDB30480 |
|---|
| PubChem Compound ID | 10903619 |
|---|
| ChEMBL ID | Not Available |
|---|
| ChemSpider ID | 9078879 |
|---|
| KEGG ID | Not Available |
|---|
| UniProt ID | Not Available |
|---|
| OMIM ID | |
|---|
| ChEBI ID | Not Available |
|---|
| BioCyc ID | Not Available |
|---|
| CTD ID | Not Available |
|---|
| Stitch ID | Not Available |
|---|
| PDB ID | Not Available |
|---|
| ACToR ID | Not Available |
|---|
| Wikipedia Link | Aflatoxin |
|---|
| References |
|---|
| Synthesis Reference | Not Available |
|---|
| MSDS | T3D3672.pdf |
|---|
| General References | - 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 ]
- Eaton DL, Gallagher EP: Mechanisms of aflatoxin carcinogenesis. Annu Rev Pharmacol Toxicol. 1994;34:135-72. [8042848 ]
- Wu Q, Jezkova A, Yuan Z, Pavlikova L, Dohnal V, Kuca K: Biological degradation of aflatoxins. Drug Metab Rev. 2009;41(1):1-7. doi: 10.1080/03602530802563850. [19514968 ]
- Peraica M, Domijan AM: Contamination of food with mycotoxins and human health. Arh Hig Rada Toksikol. 2001 Mar;52(1):23-35. [11370295 ]
- Grond S, Sablotzki A: Clinical pharmacology of tramadol. Clin Pharmacokinet. 2004;43(13):879-923. [15509185 ]
- Mullen MP, Pathak MA, West JD, Harrist TJ, Dall'Acqua F: Carcinogenic effects of monofunctional and bifunctional furocoumarins. Natl Cancer Inst Monogr. 1984 Dec;66:205-10. [6531030 ]
- Ostertag E, Becker T, Ammon J, Bauer-Aymanns H, Schrenk D: Effects of storage conditions on furocoumarin levels in intact, chopped, or homogenized parsnips. J Agric Food Chem. 2002 Apr 24;50(9):2565-70. [11958623 ]
- Santana L, Uriarte E, Roleira F, Milhazes N, Borges F: Furocoumarins in medicinal chemistry. Synthesis, natural occurrence and biological activity. Curr Med Chem. 2004 Dec;11(24):3239-61. [15579011 ]
- 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.
- Yannai, Shmuel. (2004) Dictionary of food compounds with CD-ROM: Additives, flavors, and ingredients. Boca Raton: Chapman & Hall/CRC.
- International Agency for Research on Cancer (IARC) - Summaries & Evaluations AFLATOXINS [Link]
- Aflatoxins: essential data [Link]
- Wikipedia. Aflatoxin. Last Updated 3 May 2010. [Link]
- Herboreal Ltd - Manufacturer of rare phytochemicals (2009). [Link]
- International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
- DFG Senate Commission on Food Safety (SKLM): Toxicological Assessment of Furocoumarins in Foodstuffs (2006) [Link]
|
|---|
| Gene Regulation |
|---|
| Up-Regulated Genes | Not Available |
|---|
| Down-Regulated Genes | Not Available |
|---|
