Altertoxin-1
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Basic Info
| Common Name | Altertoxin-1(F04976) |
| 2D Structure | |
| 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. (A2977, A2979) |
| FRCD ID | F04976 |
| CAS Number | 56258-32-3 |
| PubChem CID | 104860 |
| Formula | C20H16O6 |
| IUPAC Name | (12S,12aS,12bR)-4,9,12,12b-tetrahydroxy-2,11,12,12a-tetrahydro-1H-perylene-3,10-dione |
| InChI Key | GJIALGLHOBXNAT-KPOBHBOGSA-N |
| InChI | 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/t14-,19+,20-/m0/s1 |
| Canonical SMILES | C1CC2(C3C(CC(=O)C4=C(C=CC(=C34)C5=C2C(=C(C=C5)O)C1=O)O)O)O |
| Isomeric SMILES | C1C[C@]2([C@@H]3[C@H](CC(=O)C4=C(C=CC(=C34)C5=C2C(=C(C=C5)O)C1=O)O)O)O |
| Synonyms |
Altertoxin I
Altertoxin-I
CCRIS 2190
56258-32-3
3,10-Perylenedione, 1,2,11,12,12a,12b-hexahydro-1,4,9,12a-tetrahydroxy-, (1S,12aR,12bS)-
(12S,12aS,12bR)-4,9,12,12b-tetrahydroxy-2,11,12,12a-tetrahydro-1H-perylene-3,10-dione
AC1L2XMQ
(1s,12ar,12bs)-1,4,9,12a-tetrahydroxy-1,2,11,12,12a,12b-hexahydroperylene-3,10-dione
AC1Q6P81
CHEMBL521470
|
| Classifies |
Fungal Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Benzenoids |
| Class | Perylenequinones |
| Subclass | Not available |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Perylenequinones |
| Alternative Parents | |
| Molecular Framework | Aromatic homopolycyclic compounds |
| 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 |
| Description | This compound 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. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 352.342 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 0 |
| Complexity | 648 |
| Monoisotopic Mass | 352.095 |
| Exact Mass | 352.095 |
| XLogP | 1.4 |
| Formal Charge | 0 |
| Heavy Atom Count | 26 |
| Defined Atom Stereocenter Count | 3 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.7150 |
| Human Intestinal Absorption | HIA+ | 0.9589 |
| Caco-2 Permeability | Caco2+ | 0.5632 |
| P-glycoprotein Substrate | Substrate | 0.6351 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.9696 |
| Non-inhibitor | 0.9485 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.8672 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.8232 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.7848 |
| CYP450 2D6 Substrate | Non-substrate | 0.8750 |
| CYP450 3A4 Substrate | Non-substrate | 0.5000 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.5943 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.7704 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.8553 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.7798 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.7969 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.9482 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9440 |
| Non-inhibitor | 0.8023 | |
| AMES Toxicity | AMES toxic | 0.7718 |
| Carcinogens | Non-carcinogens | 0.9362 |
| Fish Toxicity | High FHMT | 0.9053 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9067 |
| Honey Bee Toxicity | High HBT | 0.6795 |
| Biodegradation | Not ready biodegradable | 0.8342 |
| Acute Oral Toxicity | III | 0.7521 |
| Carcinogenicity (Three-class) | Non-required | 0.5465 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -2.4226 | LogS |
| Caco-2 Permeability | 0.6270 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.2665 | LD50, mol/kg |
| Fish Toxicity | 0.8249 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.8717 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Chemotaxonomy of Mycotoxigenic Small-Spored <i>Alternaria</i> Fungi - Do Multitoxin Mixtures Act as an Indicator for Species Differentiation? | Front Microbiol | 2018 | 30018598 |
| Alternaria toxins in South African sunflower seeds: cooperative study. | Mycotoxin Res | 2017 Nov | 28755328 |
| Activation of the Nrf2-ARE pathway by the Alternaria alternata mycotoxins altertoxin I and II. | Arch Toxicol | 2017 Jan | 27178040 |
| Validated UPLC-MS/MS Methods To Quantitate Free and Conjugated Alternaria Toxins in Commercially Available Tomato Products and Fruit and Vegetable Juices in Belgium. | J Agric Food Chem | 2016 Jun 22 | 27180605 |
| Development of a high performance liquid chromatography tandem mass spectrometry based analysis for the simultaneous quantification of various Alternaria toxins in wine, vegetable juices and fruit juices. | J Chromatogr A | 2016 Jul 15 | 27283097 |
| Survey of Alternaria toxin contamination in food from the German market, using a rapid HPLC-MS/MS approach. | Mycotoxin Res | 2016 Feb | 26408172 |
| A new approach using micro HPLC-MS/MS for multi-mycotoxin analysis in maize samples. | Mycotoxin Res | 2015 May | 25759213 |
| Biosynthesis of seven carbon-13 labeled Alternaria toxins including altertoxins, alternariol, and alternariol methyl ether, and their application to a multiple stable isotope dilution assay. | Anal Bioanal Chem | 2015 Feb | 25577349 |
| Metabolite production by different Ulocladium species. | Int J Food Microbiol | 2008 Aug 15 | 18599140 |
| Real-time PCR quantification of the AM-toxin gene and HPLC qualification of toxigenic metabolites from Alternaria species from apples. | Int J Food Microbiol | 2006 Sep 1 | 16890318 |
| Toxigenic profile of Alternaria alternata and Alternaria radicina occurring on umbelliferous plants. | Food Addit Contam | 2005 Apr | 16019799 |
| Production of alternaria mycotoxins by Alternaria alternata isolated from weather-damaged wheat. | J Food Prot | 2001 Apr | 11307900 |
| Gas chromatography-mass spectrometry of Alternaria mycotoxins. | J Chromatogr A | 1997 Mar 28 | 9129309 |
| Mycotoxins in ingredients of animal feeding stuffs: I. Determination of Alternaria mycotoxins in oilseed rape meal and sunflower seed meal. | Food Addit Contam | 1997 Apr | 9135722 |
| Selective determination of altertoxins by high-performance liquid chromatography with electrochemical detection with dual "in-series" electrodes. | J Chromatogr | 1991 Mar 1 | 2071690 |
| Natural occurrence of Alternaria mycotoxins in sorghum and ragi from North Bihar, India. | Food Addit Contam | 1990 Nov-Dec | 2079114 |
| Profiling of Alternaria mycotoxins in foodstuffs by high-performance liquid chromatography with diode-array ultraviolet detection. | J Chromatogr | 1989 Mar 31 | 2745600 |
| Effects of purified altertoxins I, II, and III in the metabolic communication V79 system. | J Toxicol Environ Health | 1989 | 2913335 |
Targets
- 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
- Mechanism of Action:
- 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.
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 ]
- 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
- Mechanism of Action:
- 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.
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 ]
- 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
- Mechanism of Action:
- 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.
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 ]