Ochratoxin A
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Basic Info
| Common Name | Ochratoxin A(F04879) |
| 2D Structure | |
| Description | Ochratoxin A is found in barley. Mycotoxin. Ochratoxin A is produced by Aspergillus melleus, Aspergillus sulphureus and Penicillium viridicatum.Potential contaminant of foodstuffs, especially cereals. Ochratoxin A is found in stored grain products in UK (1997).Ochratoxin A, a toxin produced by Aspergillus ochraceus and Penicillium verrucosum, is one of the most abundant food-contaminating mycotoxins in the world. Human exposure occurs mainly through consumption of improperly stored food products, particularly contaminated grain and pork products, as well as coffee, wine grapes and dried grapes. The toxin has been found in the tissues and organs of animals, including human blood and breast milk. Ochratoxin A toxicity has large species- and sex-specific differences. Ochratoxin a belongs to the family of Ochratoxins and related substances. These are compounds containing the ochratoxin skeleton, which is structurally characterized by the presence of a 3-phenylpropanoic acid N-linked to a 8-hydroxy-3-methyl-1-oxo-3,4-dihydro-1H-2-benzopyran-7-carboxamide moiety[1]. (Reference: [1] http://www.inchem.org/documents/ehc/ehc/ehc105.htm). |
| FRCD ID | F04879 |
| CAS Number | 303-47-9 |
| PubChem CID | 442530 |
| Formula | C20H18ClNO6 |
| IUPAC Name | (2S)-2-[[(3R)-5-chloro-8-hydroxy-3-methyl-1-oxo-3,4-dihydroisochromene-7-carbonyl]amino]-3-phenylpropanoic acid |
| InChI Key | RWQKHEORZBHNRI-BMIGLBTASA-N |
| InChI | InChI=1S/C20H18ClNO6/c1-10-7-12-14(21)9-13(17(23)16(12)20(27)28-10)18(24)22-15(19(25)26)8-11-5-3-2-4-6-11/h2-6,9-10,15,23H,7-8H2,1H3,(H,22,24)(H,25,26)/t10-,15+/m1/s1 |
| Canonical SMILES | CC1CC2=C(C=C(C(=C2C(=O)O1)O)C(=O)NC(CC3=CC=CC=C3)C(=O)O)Cl |
| Isomeric SMILES | C[C@@H]1CC2=C(C=C(C(=C2C(=O)O1)O)C(=O)N[C@@H](CC3=CC=CC=C3)C(=O)O)Cl |
| Wikipedia | Ochratoxin A |
| Synonyms |
Ochratoxin A-BSA conjugate from Aspergillus ochraceus
OCHRATOXIN A
Antibiotic 9663
303-47-9
Phenylalanine - ochratoxin A
3R14S-Ochratoxin A
NCI-C56586
C20H18ClNO6
CHEBI:7719
RWQKHEORZBHNRI-BMIGLBTASA-N
|
| Classifies |
Fungal Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Phenylpropanoids and polyketides |
| Class | Ochratoxins and related substances |
| Subclass | Not available |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Ochratoxins and related substances |
| Alternative Parents |
|
| Molecular Framework | Aromatic heteropolycyclic compounds |
| Substituents | Ochratoxin-skeleton - Phenylalanine or derivatives - N-acyl-alpha amino acid or derivatives - N-acyl-alpha-amino acid - 3-phenylpropanoic-acid - Alpha-amino acid or derivatives - Amphetamine or derivatives - Salicylic acid or derivatives - 2-benzopyran - Isochromane - Benzopyran - Aryl halide - Benzenoid - Aryl chloride - Dicarboxylic acid or derivatives - Monocyclic benzene moiety - Vinylogous acid - Carboxamide group - Carboxylic acid ester - Secondary carboxylic acid amide - Lactone - Carboxylic acid - Carboxylic acid derivative - Organoheterocyclic compound - Oxacycle - Organopnictogen compound - Organic oxygen compound - Organic nitrogen compound - Carbonyl group - Hydrocarbon derivative - Organic oxide - Organooxygen compound - Organonitrogen compound - Organochloride - Organohalogen compound - Aromatic heteropolycyclic compound |
| Description | This compound belongs to the class of organic compounds known as ochratoxins and related substances. These are a group of chemically related metabolites containing a 3,4-dihydro-3-methylisocoumarin moiety linked through a carboxyl group to L-beta-phenylalanine by a secondary amine bond. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 403.815 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 5 |
| Complexity | 608 |
| Monoisotopic Mass | 403.082 |
| Exact Mass | 403.082 |
| XLogP | 4.7 |
| Formal Charge | 0 |
| Heavy Atom Count | 28 |
| Defined Atom Stereocenter Count | 2 |
| 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- | 0.7921 |
| Human Intestinal Absorption | HIA+ | 0.6933 |
| Caco-2 Permeability | Caco2- | 0.6992 |
| P-glycoprotein Substrate | Substrate | 0.6252 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.9450 |
| Non-inhibitor | 0.9769 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.9424 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.4468 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.6608 |
| CYP450 2D6 Substrate | Non-substrate | 0.8191 |
| CYP450 3A4 Substrate | Substrate | 0.5745 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.7699 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.8041 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.8190 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.7773 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.8095 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.6991 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9541 |
| Non-inhibitor | 0.9187 | |
| AMES Toxicity | Non AMES toxic | 0.9132 |
| Carcinogens | Non-carcinogens | 0.9295 |
| Fish Toxicity | High FHMT | 0.9587 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9935 |
| Honey Bee Toxicity | Low HBT | 0.7652 |
| Biodegradation | Not ready biodegradable | 0.9635 |
| Acute Oral Toxicity | I | 0.8259 |
| Carcinogenicity (Three-class) | Danger | 0.7626 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -4.0879 | LogS |
| Caco-2 Permeability | -0.2707 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 4.2736 | LD50, mol/kg |
| Fish Toxicity | 0.8535 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.4741 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Simultaneous determination of trace Aflatoxin B<sub>1</sub> and Ochratoxin A by aptamer-based microchip capillary electrophoresis in food samples. | J Chromatogr A | 2018 Sep 28 | 30037541 |
| Determination of Ochratoxin A traces in foodstuffs: Comparison of an automated on-line two-dimensional high-performance liquid chromatography and off-line immunoaffinity-high-performance liquid chromatography system. | J Chromatogr A | 2018 Sep 28 | 30054130 |
| Precision toxicology shows that troxerutin alleviates ochratoxin A-induced renal lipotoxicity. | FASEB J | 2018 Sep 24 | 30247986 |
| Contaminants in Grain-A Major Risk for Whole Grain Safety? | Nutrients | 2018 Sep 2 | 30200531 |
| Interaction of 2'R-ochratoxin A with Serum Albumins: Binding Site, Effects of Site Markers, Thermodynamics, Species Differences of Albumin-binding, and Influence of Albumin on Its Toxicity in MDCK Cells. | Toxins (Basel) | 2018 Sep 1 | 30200461 |
| Mycotoxins in infant/toddler foods and breakfast cereals in the US retail market. | Food Addit Contam Part B Surveill | 2018 Sep | 29575988 |
| Co-occurrence of mycotoxins in commercial formula milk and cereal-based baby food on the Qatar market. | Food Addit Contam Part B Surveill | 2018 Sep | 29490584 |
| Protective effects of compound ammonium glycyrrhizin, L‑arginine, silymarin and glucurolactone against liver damage induced by ochratoxin A in primary chicken hepatocytes. | Mol Med Rep | 2018 Sep | 30015927 |
| Restorative effect of l-Dopa treatment against Ochratoxin A induced neurotoxicity. | Neurochem Int | 2018 Sep | 29627381 |
| Reduced graphene oxide and gold nanoparticle composite-based solid-phase extraction coupled with ultra-high-performance liquid chromatography-tandem mass spectrometry for the determination of 9 mycotoxins in milk. | Food Chem | 2018 Oct 30 | 29853368 |
| An ultrasensitive signal-on electrochemical aptasensor for ochratoxin A determination based on DNA controlled layer-by-layer assembly of dual gold nanoparticle conjugates. | Biosens Bioelectron | 2018 Oct 15 | 30096739 |
| Application of Stable Isotope Dilution and Liquid Chromatography Tandem Mass Spectrometry for Multi-Mycotoxin Analysis in Edible Oils. | J AOAC Int | 2018 Oct 10 | 30305203 |
| An ITO-based point-of-care colorimetric immunosensor for ochratoxin A detection. | Talanta | 2018 Oct 1 | 30029418 |
| Fabrication of a novel and high-performance amperometric sensor for highly sensitive determination of ochratoxin A in juice samples. | Talanta | 2018 Oct 1 | 30029368 |
| Polymeric substances for the removal of ochratoxin A from red wine followed by computational modeling of the complexes formed. | Food Chem | 2018 Nov 1 | 29884367 |
| Mycotoxins induce developmental toxicity and behavioural aberrations in zebrafish larvae. | Environ Pollut | 2018 Nov | 30005262 |
| Effects of dietary deoxynivalenol or ochratoxin A on performance and selected health indices in Atlantic salmon (Salmo salar). | Food Chem Toxicol | 2018 Nov | 30179646 |
| OTA induces intestinal epithelial barrier dysfunction and tight junction disruption in IPEC-J2 cells through ROS/Ca<sup>2+</sup>-mediated MLCK activation. | Environ Pollut | 2018 Nov | 29966834 |
| A reproductive and developmental screening study of the fungal toxin ochratoxin A in Fischer rats. | Mycotoxin Res | 2018 Nov | 29971579 |
| Mitigation of cell apoptosis induced by ochratoxin A (OTA) is possibly through organic cation transport 2 (OCT2) knockout. | Food Chem Toxicol | 2018 Nov | 30120945 |
Targets
- General Function:
- Ubiquinone binding
- Specific Function:
- Iron-sulfur protein (IP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
- Gene Name:
- SDHB
- Uniprot ID:
- P21912
- Molecular Weight:
- 31629.365 Da
- Mechanism of Action:
- Ochratoxin A is an uncompetitive inhibitor of succinate dehydrogenase.
References
- Wei YH, Lu CY, Lin TN, Wei RD: Effect of ochratoxin A on rat liver mitochondrial respiration and oxidative phosphorylation. Toxicology. 1985 Aug;36(2-3):119-30. [2996181 ]
- General Function:
- Steroid hydroxylase activity
- Specific Function:
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
- Gene Name:
- CYP2C9
- Uniprot ID:
- P11712
- Molecular Weight:
- 55627.365 Da
- Mechanism of Action:
- Some cytochrome P-450 enzymes, such as CYP2C9, are known to metabolize ochratoxin A into more cytotoxic compounds capable of forming DNA adducts.
References
- Simarro Doorten AY, Bull S, van der Doelen MA, Fink-Gremmels J: Metabolism-mediated cytotoxicity of ochratoxin A. Toxicol In Vitro. 2004 Jun;18(3):271-7. [15046773 ]
- General Function:
- Phosphoenolpyruvate carboxykinase (gtp) activity
- Specific Function:
- Catalyzes the conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle.
- Gene Name:
- PCK1
- Uniprot ID:
- P35558
- Molecular Weight:
- 69193.975 Da
- Mechanism of Action:
- Ochratoxin A is an inhibitor of renal phosphoenolpyruvate carboxykinase.
References
- Meisner H, Meisner P: Ochratoxin A, an in vivo inhibitor of renal phosphoenolpyruvate carboxykinase. Arch Biochem Biophys. 1981 Apr 15;208(1):146-53. [7259174 ]
- General Function:
- Ubiquinone binding
- Specific Function:
- Membrane-anchoring subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
- Gene Name:
- SDHD
- Uniprot ID:
- O14521
- Molecular Weight:
- 17042.82 Da
- Mechanism of Action:
- Ochratoxin A is an uncompetitive inhibitor of succinate dehydrogenase.
References
- Wei YH, Lu CY, Lin TN, Wei RD: Effect of ochratoxin A on rat liver mitochondrial respiration and oxidative phosphorylation. Toxicology. 1985 Aug;36(2-3):119-30. [2996181 ]