Alternariol
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Basic Info
| Common Name | Alternariol(F04974) |
| 2D Structure | |
| Description | Alternariol is found in mushrooms. Alternariol occurs in mycelium of Alternaria tenuis responsible for alternaria cone disorder in hops and fruit spot on papaya (Carica papaya) and Passiflora species.Alternariol is a toxic metabolite of Alternaria fungi. It is an important contaminant in cereals and fruits. Alternariol belongs to the family of Isocoumarins and Derivatives. These are polycyclic compounds containing an isochromane which bears a ketone at the carbon C1. |
| FRCD ID | F04974 |
| CAS Number | 641-38-3 |
| PubChem CID | 5359485 |
| Formula | C14H10O5 |
| IUPAC Name | 3,7,9-trihydroxy-1-methylbenzo[c]chromen-6-one |
| InChI Key | CEBXXEKPIIDJHL-UHFFFAOYSA-N |
| InChI | InChI=1S/C14H10O5/c1-6-2-7(15)5-11-12(6)9-3-8(16)4-10(17)13(9)14(18)19-11/h2-5,15-17H,1H3 |
| Canonical SMILES | CC1=CC(=CC2=C1C3=CC(=CC(=C3C(=O)O2)O)O)O |
| Isomeric SMILES | CC1=CC(=CC2=C1C3=CC(=CC(=C3C(=O)O2)O)O)O |
| Wikipedia | Alternariol |
| Synonyms |
Alternariol
641-38-3
UNII-KN9L4260JW
CCRIS 6734
AOH
BRN 0244839
3,7,9-Trihydroxy-1-methyl-6H-benzo[c]chromen-6-one
KN9L4260JW
Alternariol from Alternaria sp.
CHEBI:64983
|
| Classifies |
Fungal Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Phenylpropanoids and polyketides |
| Class | Coumarins and derivatives |
| Subclass | Not available |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Coumarins and derivatives |
| Alternative Parents | |
| Molecular Framework | Aromatic heteropolycyclic compounds |
| Substituents | Coumarin - Isocoumarin - Benzopyran - 1-benzopyran - 2-benzopyran - 1-hydroxy-4-unsubstituted benzenoid - 1-hydroxy-2-unsubstituted benzenoid - Pyranone - Pyran - Benzenoid - Heteroaromatic compound - Vinylogous acid - Lactone - Oxacycle - Polyol - Organoheterocyclic compound - Organooxygen compound - Hydrocarbon derivative - Organic oxide - Organic oxygen compound - Aromatic heteropolycyclic compound |
| Description | This compound 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). |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 258.229 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 0 |
| Complexity | 371 |
| Monoisotopic Mass | 258.053 |
| Exact Mass | 258.053 |
| XLogP | 2.9 |
| Formal Charge | 0 |
| Heavy Atom Count | 19 |
| Defined Atom Stereocenter Count | 0 |
| 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+ | 0.5482 |
| Human Intestinal Absorption | HIA+ | 0.9358 |
| Caco-2 Permeability | Caco2+ | 0.9020 |
| P-glycoprotein Substrate | Substrate | 0.5630 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.9679 |
| Non-inhibitor | 0.9513 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.9026 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.5694 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.7189 |
| CYP450 2D6 Substrate | Non-substrate | 0.9014 |
| CYP450 3A4 Substrate | Non-substrate | 0.6705 |
| CYP450 1A2 Inhibitor | Inhibitor | 0.7511 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.7467 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9402 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.8813 |
| CYP450 3A4 Inhibitor | Inhibitor | 0.7556 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.6794 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9412 |
| Non-inhibitor | 0.9415 | |
| AMES Toxicity | Non AMES toxic | 0.9133 |
| Carcinogens | Non-carcinogens | 0.9347 |
| Fish Toxicity | High FHMT | 0.7510 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.8294 |
| Honey Bee Toxicity | High HBT | 0.7609 |
| Biodegradation | Not ready biodegradable | 0.6725 |
| Acute Oral Toxicity | III | 0.8271 |
| Carcinogenicity (Three-class) | Non-required | 0.5806 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -2.8059 | LogS |
| Caco-2 Permeability | 0.7249 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.0795 | LD50, mol/kg |
| Fish Toxicity | 1.0234 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.0675 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Development and Application of a QuEChERS-Based Liquid Chromatography Tandem Mass Spectrometry Method to Quantitate Multi-Component <i>Alternaria</i> Toxins in Jujube. | Toxins (Basel) | 2018 Sep 21 | 30248926 |
| First insights into Alternaria multi-toxin in vivo metabolism. | Toxicol Lett | 2018 Oct 12 | 30321595 |
| An integrated in silico/in vitro approach to assess the xenoestrogenic potential of Alternaria mycotoxins and metabolites. | Food Chem | 2018 May 15 | 29329852 |
| Optimized QuEChERS Method Combined with UHPLC-MS/MS for the Simultaneous Determination of 15 Mycotoxins in Liquorice. | J AOAC Int | 2018 May 1 | 29073944 |
| Simple Approach for the Rapid Detection of Alternariol in Pear Fruit by Surface-Enhanced Raman Scattering with Pyridine-Modified Silver Nanoparticles. | J Agric Food Chem | 2018 Mar 7 | 29443523 |
| Mycotoxin production of Alternaria strains isolated from Korean barley grains determined by LC-MS/MS. | Int J Food Microbiol | 2018 Mar 2 | 29328967 |
| Analysis of alternariol and alternariol monomethyl ether in foodstuffs by molecularly imprinted solid-phase extraction and ultra-high-performance liquid chromatography tandem mass spectrometry. | Food Chem | 2018 Mar 15 | 29146349 |
| Mycotoxin contamination of sorghum and its contribution to human dietary exposure in four sub-Saharan countries. | Food Addit Contam Part A Chem Anal Control Expo Risk Assess | 2018 Jul | 29912638 |
| Tracking emerging mycotoxins in food: development of an LC-MS/MS method for free and modified Alternaria toxins. | Anal Bioanal Chem | 2018 Jul | 29766221 |
| Predominant mycotoxins, mycotoxigenic fungi and climate change related to wine. | Food Res Int | 2018 Jan | 29389638 |
| Survey of roasted street-vended nuts in Sierra Leone for toxic metabolites of fungal origin. | Food Addit Contam Part A Chem Anal Control Expo Risk Assess | 2018 Aug | 29787353 |
| High resolution-ion mobility mass spectrometry as an additional powerful tool for structural characterization of mycotoxin metabolites. | Food Chem | 2018 Apr 15 | 29287439 |
| Stability of alternariol and alternariol monomethyl ether during food processing of tomato products. | Food Chem | 2018 Apr 15 | 29287464 |
| Determination of four Alternaria alternata mycotoxins by QuEChERS approachcoupled with liquid chromatography-tandem mass spectrometry in tomato-based andfruit-based products. | Food Res Int | 2018 Apr | 29579974 |
| Chemotaxonomy of Mycotoxigenic Small-Spored <i>Alternaria</i> Fungi - Do Multitoxin Mixtures Act as an Indicator for Species Differentiation? | Front Microbiol | 2018 | 30018598 |
| Metabolic Profiling on Alternaria Toxins and Components of Xinjiang Jujubes Incubated with Pathogenic Alternaria alternata and Alternaria tenuissima via Orbitrap High-Resolution Mass Spectrometry. | J Agric Food Chem | 2017 Sep 27 | 28882039 |
| Awareness and Prevalence of Mycotoxin Contamination in Selected Nigerian Fermented Foods. | Toxins (Basel) | 2017 Nov 8 | 29117141 |
| Alternaria toxins in South African sunflower seeds: cooperative study. | Mycotoxin Res | 2017 Nov | 28755328 |
| Multi-mycotoxin analysis using dried blood spots and dried serum spots. | Anal Bioanal Chem | 2017 May | 28299415 |
| Synergistic estrogenic effects of Fusarium and Alternaria mycotoxins in vitro. | Arch Toxicol | 2017 Mar | 27401186 |
Targets
- General Function:
- Serine hydrolase activity
- Specific Function:
- Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
- Gene Name:
- ACHE
- Uniprot ID:
- P22303
- Molecular Weight:
- 67795.525 Da
- Mechanism of Action:
- Alternariol competitively inhibits acetylcholinesterase.
References
- 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 ]
- 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:
- Alternariol 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:
- 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:
- Alternariol 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:
- Alternariol 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:
- Zinc ion binding
- Specific Function:
- Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner (PubMed:20074560). Isoform beta-cx lacks ligand binding ability and has no or only very low ere binding activity resulting in the loss of ligand-dependent transactivation ability. DNA-binding by ESR1 and ESR2 is rapidly lost at 37 degrees Celsius in the absence of ligand while in the presence of 17 beta-estradiol and 4-hydroxy-tamoxifen loss in DNA-binding at elevated temperature is more gradual.
- Gene Name:
- ESR2
- Uniprot ID:
- Q92731
- Molecular Weight:
- 59215.765 Da
- Mechanism of Action:
- Alternariol is able to act as an agonist at estrogen receptors.
References
- 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 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
- Gene Name:
- ESR1
- Uniprot ID:
- P03372
- Molecular Weight:
- 66215.45 Da
- Mechanism of Action:
- Alternariol is able to act as an agonist at estrogen receptors.
References
- 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 ]