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T3D3729 - Altertoxin-1
| Record Information | |
|---|---|
| Version | 1.0 |
| Creation Date | 2010-05-04 18:46:42 UTC |
| Update Date | 2013-04-25 08:48:46 UTC |
| Accession Number | T3D3729 |
| Identification | |
| Common Name | Altertoxin-1 |
| 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. (W827, W829) |
| Compound Type |
|
| Chemical Structure |
|
| Synonyms |
|
| Chemical Formula | C20H16O6 |
| Average Molecular Weight | 352.3374 |
| Monoisotopic Molecular Weight | 352.094688244 |
| Chemical IUPAC Name | 1,4,9,12a-tetrahydroxy-2,11,12,12b-tetrahydro-1H-perylene-3,10-dione |
| CAS Registry Number | 56258-32-3 |
| 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 | |
| Kingdom | Organic Compounds |
| Super Class | Benzenoids |
| Class | Phenanthrenes and Derivatives |
| Sub Class | Not Available |
| Direct Parent | Phenanthrenes and Derivatives |
| Alternative Parents |
|
| Molecular Framework | Aromatic Homopolycyclic Compounds |
| Substituents |
|
| External Descriptors | Not Available |
| External Links | |
| DrugBank ID | Not Available |
| PubChem Compound ID | 104860  |
| KEGG ID | Not Available |
| UniProt ID | Not Available |
| OMIM ID | Not Available |
| 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 |
| Physical Properties | |
| Appearance | Not Available |
| Melting Point | Not Available |
| Solubility | Not Available |
| Predicted LogP | 1.8796728243333336 |
| Toxicity Profile | |
| Route of Exposure | Oral, dermal, inhalation, and parenteral (contaminated drugs). (W967) |
| Mechanism of Action | 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. (W827, W828, W829) |
| Metabolism | Not Available |
| Toxicity Values | Not Available |
| Lethal Dose | Not Available |
| Carcinogenicity (IARC Classification) | Not Available |
| 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. (W827, W829) |
| 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. (W827, W829) |
| Symptoms | Not Available |
| Treatment | Not Available |
| References | |
| General References |
|
Targets
1. Cytokine receptor common subunit beta
High affinity receptor for interleukin-3, interleukin-5 and granulocyte-macrophage colony-stimulating factor.
Altertoxin-1 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. (W827, W828, W829)UniProt ID: P32927
Gene: CSF2RB
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- W828 — 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 ]
- W829 — 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 ]
- W827 — Fehr M, Pahlke G, Fritz J, Christensen MO, Boege F, Altemöller 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.
[18727009 ]
2. DNA topoisomerase 1
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.
Altertoxin-1 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. (W827, W828, W829)UniProt ID: P11387
Gene: TOP1
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- W827 — Fehr M, Pahlke G, Fritz J, Christensen MO, Boege F, Altemöller 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.
[18727009 ]
- W828 — 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 ]
- W829 — 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 ]
3. DNA topoisomerase 2-alpha
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.
Altertoxin-1 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. (W827, W828, W829)UniProt ID: P11388
Gene: TOP2A
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- W827 — Fehr M, Pahlke G, Fritz J, Christensen MO, Boege F, Altemöller 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.
[18727009 ]
- W828 — 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 ]
- W829 — 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 ]
4. DNA topoisomerase 2-beta
Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Indirectly involved in vitamin D-coupled transcription regulation via its association with the WINAC complex, a chromatin-remodeling complex recruited by vitamin D receptor (VDR), which is required for the ligand-bound VDR-mediated transrepression of the CYP27B1 gene.
Altertoxin-1 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. (W827, W828, W829)UniProt ID: Q02880
Gene: TOP2B
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report
References:
- W827 — Fehr M, Pahlke G, Fritz J, Christensen MO, Boege F, Altemöller 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.
[18727009 ]
- W828 — 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 ]
- W829 — 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 ]