T3DB: Alternariol methyl ether

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

2010-05-04 17:21:10 UTC

Update Date

2014-12-24 20:26:27 UTC

Accession Number

T3D3728

Identification

Common Name

Alternariol methyl ether

Class

Small Molecule

Description

Alternariol methyl ether is an altertoxin, which is a mycotoxin of Alternaria fungi. Altertoxins are important contaminants in cereals, vegetables, and fruits, as well as in the ground, on wood or walls. Studies have shown altertoxins to be toxic, genotoxic, mutagenic, and carcinogenic. In particular, they have been associated with esophageal cancer in humans. (1, 3)

Compound Type

Ester
Ether
Fungal Toxin
Mycotoxin
Natural Compound
Organic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
2-Biphenylcarboxylic acid, 2',3',4'-trihydroxy-5-methoxy-6'-methyl-, delta-lactone
2-Biphenylcarboxylic acid, 2',3',4'-trihydroxy-5-methoxy-6'-methyl-, delta-lactone (6CI)
3,7-Dihydroxy-9-methoxy-1-methyl-6H-benzo[c]chromen-6-one
3,7-Dihydroxy-9-methoxy-1-methyl-6H-dibenzo(b,d)pyran-6-one
alternariol 5-O-methyl ether
Alternariol monomethyl ether
Alternariol monomethylether
Alternariol-9-methyl ether
AME
Djalonensone

Chemical Formula

C₁₅H₁₂O₅

Average Molecular Mass

272.253 g/mol

Monoisotopic Mass

272.068 g/mol

CAS Registry Number

23452-05-3

IUPAC Name

3,7-dihydroxy-9-methoxy-1-methyl-6H-benzo[c]chromen-6-one

Traditional Name

3,7-dihydroxy-9-methoxy-1-methylbenzo[c]chromen-6-one

SMILES

COC1=CC(O)=C2C(=O)OC3=C(C(C)=CC(O)=C3)C2=C1

InChI Identifier

InChI=1S/C15H12O5/c1-7-3-8(16)4-12-13(7)10-5-9(19-2)6-11(17)14(10)15(18)20-12/h3-6,16-17H,1-2H3

InChI Key

InChIKey=LCSDQFNUYFTXMT-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as coumarins and derivatives. These are polycyclic aromatic compounds containing a 1-benzopyran moiety with a ketone group at the C2 carbon atom (1-benzopyran-2-one).

Kingdom

Organic compounds

Super Class

Phenylpropanoids and polyketides

Class

Coumarins and derivatives

Sub Class

Not Available

Direct Parent

Coumarins and derivatives

Alternative Parents

Substituents

Coumarin
Isocoumarin
Benzopyran
2-benzopyran
1-benzopyran
Anisole
1-hydroxy-4-unsubstituted benzenoid
1-hydroxy-2-unsubstituted benzenoid
Alkyl aryl ether
Pyranone
Benzenoid
Pyran
Heteroaromatic compound
Vinylogous acid
Lactone
Oxacycle
Ether
Organoheterocyclic compound
Organic oxygen compound
Hydrocarbon derivative
Organic oxide
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

Membrane

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

White powder.

Experimental Properties

Property	Value
Melting Point	Not Available
Boiling Point	Not Available
Solubility	Not Available
LogP	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.09 g/L	ALOGPS
logP	2.25	ALOGPS
logP	3.32	ChemAxon
logS	-3.5	ALOGPS
pKa (Strongest Acidic)	7.71	ChemAxon
pKa (Strongest Basic)	-4.1	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	4	ChemAxon
Hydrogen Donor Count	2	ChemAxon
Polar Surface Area	75.99 Å²	ChemAxon
Rotatable Bond Count	1	ChemAxon
Refractivity	72.41 m³·mol⁻¹	ChemAxon
Polarizability	27.25 Å³	ChemAxon
Number of Rings	3	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
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-00di-0090000000-9dff801a2758792e7269	2016-06-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-00di-0090000000-607a288b5f5a34f0a6c9	2016-06-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0a6u-1090000000-f0add938f0e76c07dcce	2016-06-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-00di-0090000000-7173b22425d15c235102	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-00di-0090000000-68d751616f54427bceab	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-006y-2290000000-c7c7120ed9225f2b0ec5	2016-08-03	View Spectrum

Toxicity Profile

Route of Exposure

Oral, dermal, inhalation, and parenteral (contaminated drugs). (5)

Mechanism of Toxicity

Alternariol methyl ether has been shown to have genotoxic and mutagenic properties. It has demonstrated DNA-damaging activities such as single-strand and double-strand DNA breaks, DNA-intercalating, and DNA cross-linking, as well as induction of DNA repair synthesis and inhibition of DNA replication. These effects are thought to be at least partially due to its ability to bind to the DNA minor groove with high affinity, which inhibits the activity of DNA-acting enzymes such as topoisomerase. (1, 2, 3)

Metabolism

Alternariol methyl ether is metabolized by microsomes in the liver, preferentially at aromatic positions. It is also demethylated to alternariol. The products of aromatic hydroxylation are either catechols or hydroquinones, which may form reactive semiquinones and quinones or undergo redox cycling. (4)

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

Not listed by IARC.

Uses/Sources

Minimum Risk Level

Not Available

Health Effects

Altertoxins have been shown to be toxic, genotoxic, mutagenic, and carcinogenic. In particular, they have been associated with esophageal cancer in humans. (1, 3)

Symptoms

Not Available

Treatment

Not Available

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

Not Available

HMDB ID

Not Available

PubChem Compound ID

5360741

ChEMBL ID

CHEMBL483526

ChemSpider ID

4514573

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

Not Available

References

Synthesis Reference

Not Available

MSDS

T3D3728.pdf

General References

Fehr M, Pahlke G, Fritz J, Christensen MO, Boege F, Altemoller M, Podlech J, Marko D: Alternariol acts as a topoisomerase poison, preferentially affecting the IIalpha isoform. Mol Nutr Food Res. 2009 Apr;53(4):441-51. doi: 10.1002/mnfr.200700379. [18727009 ]
Brugger EM, Wagner J, Schumacher DM, Koch K, Podlech J, Metzler M, Lehmann L: Mutagenicity of the mycotoxin alternariol in cultured mammalian cells. Toxicol Lett. 2006 Jul 14;164(3):221-30. Epub 2006 Feb 7. [16464542 ]
Lehmann L, Wagner J, Metzler M: Estrogenic and clastogenic potential of the mycotoxin alternariol in cultured mammalian cells. Food Chem Toxicol. 2006 Mar;44(3):398-408. Epub 2005 Sep 27. [16194592 ]
Pfeiffer E, Schebb NH, Podlech J, Metzler M: Novel oxidative in vitro metabolites of the mycotoxins alternariol and alternariol methyl ether. Mol Nutr Food Res. 2007 Mar;51(3):307-16. [17340575 ]
Peraica M, Domijan AM: Contamination of food with mycotoxins and human health. Arh Hig Rada Toksikol. 2001 Mar;52(1):23-35. [11370295 ]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. DNA topoisomerase 1

General Function:: Poly(a) rna binding
Specific Function:: Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone (By similarity). Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. Involved in the circadian transcription of the core circadian clock component ARNTL/BMAL1 by altering the chromatin structure around the ROR response elements (ROREs) on the ARNTL/BMAL1 promoter.
Gene Name:: TOP1
Uniprot ID:: P11387
Molecular Weight:: 90725.19 Da

References

Fehr M, Pahlke G, Fritz J, Christensen MO, Boege F, Altemoller M, Podlech J, Marko D: Alternariol acts as a topoisomerase poison, preferentially affecting the IIalpha isoform. Mol Nutr Food Res. 2009 Apr;53(4):441-51. doi: 10.1002/mnfr.200700379. [18727009 ]
Brugger EM, Wagner J, Schumacher DM, Koch K, Podlech J, Metzler M, Lehmann L: Mutagenicity of the mycotoxin alternariol in cultured mammalian cells. Toxicol Lett. 2006 Jul 14;164(3):221-30. Epub 2006 Feb 7. [16464542 ]
Lehmann L, Wagner J, Metzler M: Estrogenic and clastogenic potential of the mycotoxin alternariol in cultured mammalian cells. Food Chem Toxicol. 2006 Mar;44(3):398-408. Epub 2005 Sep 27. [16194592 ]

2. 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

Brugger EM, Wagner J, Schumacher DM, Koch K, Podlech J, Metzler M, Lehmann L: Mutagenicity of the mycotoxin alternariol in cultured mammalian cells. Toxicol Lett. 2006 Jul 14;164(3):221-30. Epub 2006 Feb 7. [16464542 ]
Lehmann L, Wagner J, Metzler M: Estrogenic and clastogenic potential of the mycotoxin alternariol in cultured mammalian cells. Food Chem Toxicol. 2006 Mar;44(3):398-408. Epub 2005 Sep 27. [16194592 ]
Fehr M, Pahlke G, Fritz J, Christensen MO, Boege F, Altemoller M, Podlech J, Marko D: Alternariol acts as a topoisomerase poison, preferentially affecting the IIalpha isoform. Mol Nutr Food Res. 2009 Apr;53(4):441-51. doi: 10.1002/mnfr.200700379. [18727009 ]

Target Details

3. DNA topoisomerase 2-alpha

General Function:: Ubiquitin binding
Specific Function:: Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segregation of daughter chromosomes. May play a role in regulating the period length of ARNTL/BMAL1 transcriptional oscillation (By similarity).
Gene Name:: TOP2A
Uniprot ID:: P11388
Molecular Weight:: 174383.88 Da

References

Fehr M, Pahlke G, Fritz J, Christensen MO, Boege F, Altemoller M, Podlech J, Marko D: Alternariol acts as a topoisomerase poison, preferentially affecting the IIalpha isoform. Mol Nutr Food Res. 2009 Apr;53(4):441-51. doi: 10.1002/mnfr.200700379. [18727009 ]
Brugger EM, Wagner J, Schumacher DM, Koch K, Podlech J, Metzler M, Lehmann L: Mutagenicity of the mycotoxin alternariol in cultured mammalian cells. Toxicol Lett. 2006 Jul 14;164(3):221-30. Epub 2006 Feb 7. [16464542 ]
Lehmann L, Wagner J, Metzler M: Estrogenic and clastogenic potential of the mycotoxin alternariol in cultured mammalian cells. Food Chem Toxicol. 2006 Mar;44(3):398-408. Epub 2005 Sep 27. [16194592 ]

Target Details

4. DNA topoisomerase 2-beta

General Function:: Protein kinase c binding
Specific Function:: Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks.
Gene Name:: TOP2B
Uniprot ID:: Q02880
Molecular Weight:: 183265.825 Da

References

Fehr M, Pahlke G, Fritz J, Christensen MO, Boege F, Altemoller M, Podlech J, Marko D: Alternariol acts as a topoisomerase poison, preferentially affecting the IIalpha isoform. Mol Nutr Food Res. 2009 Apr;53(4):441-51. doi: 10.1002/mnfr.200700379. [18727009 ]
Brugger EM, Wagner J, Schumacher DM, Koch K, Podlech J, Metzler M, Lehmann L: Mutagenicity of the mycotoxin alternariol in cultured mammalian cells. Toxicol Lett. 2006 Jul 14;164(3):221-30. Epub 2006 Feb 7. [16464542 ]
Lehmann L, Wagner J, Metzler M: Estrogenic and clastogenic potential of the mycotoxin alternariol in cultured mammalian cells. Food Chem Toxicol. 2006 Mar;44(3):398-408. Epub 2005 Sep 27. [16194592 ]

Alternariol methyl ether (T3D3728)

Structure for T3D3728: Alternariol methyl ether

Targets

References

References

References

References