T3DB: Altertoxin-1

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 18:46:42 UTC

Update Date

2014-12-24 20:26:27 UTC

Accession Number

T3D3729

Identification

Common Name

Altertoxin-1

Class

Small Molecule

Description

Altertoxin-1 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. (2, 3)

Compound Type

Ester
Fungal Toxin
Mycotoxin
Natural Compound
Organic Compound

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
Altertoxin I
Altertoxin-I

Chemical Formula

C₂₀H₁₆O₆

Average Molecular Mass

352.337 g/mol

Monoisotopic Mass

352.095 g/mol

CAS Registry Number

56258-32-3

IUPAC Name

1,4,9,12a-tetrahydroxy-1,2,3,10,11,12,12a,12b-octahydroperylene-3,10-dione

Traditional Name

1,4,9,12a-tetrahydroxy-2,11,12,12b-tetrahydro-1H-perylene-3,10-dione

SMILES

OC1CC(=O)C2=C(O)C=CC3=C2C1C1(O)CCC(=O)C2=C(O)C=CC3=C12

InChI Identifier

InChI=1S/C20H16O6/c21-10-3-1-8-9-2-4-11(22)17-12(23)5-6-20(26,18(9)17)19-14(25)7-13(24)16(10)15(8)19/h1-4,14,19,21-22,25-26H,5-7H2

InChI Key

InChIKey=GJIALGLHOBXNAT-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as perylenequinones. These are heterocyclic compounds characterized by two 8-hydroxy-1,4-dihydronaphthalen-1-one moieties joined together one or two CC-bonds.

Kingdom

Organic compounds

Super Class

Benzenoids

Class

Perylenequinones

Sub Class

Not Available

Direct Parent

Perylenequinones

Alternative Parents

Substituents

Perylenequinone
Phenanthrene
Naphthalene
Tetralin
Aryl alkyl ketone
Aryl ketone
1-hydroxy-2-unsubstituted benzenoid
Tertiary alcohol
Vinylogous acid
Secondary alcohol
Ketone
Polyol
Hydrocarbon derivative
Organic oxide
Organooxygen compound
Organic oxygen compound
Alcohol
Aromatic homopolycyclic compound

Molecular Framework

Aromatic homopolycyclic compounds

External Descriptors

Not Available

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

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	0.64 g/L	ALOGPS
logP	1.55	ALOGPS
logP	1.88	ChemAxon
logS	-2.7	ALOGPS
pKa (Strongest Acidic)	9.44	ChemAxon
pKa (Strongest Basic)	-3	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	6	ChemAxon
Hydrogen Donor Count	4	ChemAxon
Polar Surface Area	115.06 Å²	ChemAxon
Rotatable Bond Count	0	ChemAxon
Refractivity	92.65 m³·mol⁻¹	ChemAxon
Polarizability	35.22 Å³	ChemAxon
Number of Rings	5	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	splash10-0f79-0009000000-5dcb700a5afd8a3c30f4	2016-06-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0ftr-0139000000-714b50ec8b4b62c22176	2016-06-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-014i-2159000000-a28dfdf98902770b6e50	2016-06-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0udi-0009000000-c66e7a66d48c5ebf7b2d	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0ue9-0029000000-73ed6ba6c7d445a3c1ac	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-056r-2097000000-0ec16c11c9975a8ccd2b	2016-08-03	View Spectrum

Toxicity Profile

Route of Exposure

Oral, dermal, inhalation, and parenteral (contaminated drugs). (1)

Mechanism of Toxicity

Altertoxin-1 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. (2, 4, 3)

Metabolism

Not Available

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

Not listed by IARC.

Uses/Sources

Altertoxin-1 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. (2, 3)

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. (2, 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

104860

ChEMBL ID

Not Available

ChemSpider ID

26286836

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

Not Available

General References

Peraica M, Domijan AM: Contamination of food with mycotoxins and human health. Arh Hig Rada Toksikol. 2001 Mar;52(1):23-35. [11370295 ]
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 ]
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 ]
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 ]

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

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

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 ]

Altertoxin-1 (T3D3729)

Structure for T3D3729: Altertoxin-1

Targets

References

References

References

References