Trichothecin
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Basic Info
| Common Name | Trichothecin(F04965) |
| 2D Structure | |
| Description | Trichothecin is a trichothecene. Trichothecenes are a very large family of chemically related mycotoxins produced by various species of Fusarium, Myrothecium, Trichoderma, Trichothecium, Cephalosporium, Verticimonosporium, and Stachybotrys. The most important structural features causing the biological activities of trichothecenes are: the 12,13-epoxy ring, the presence of hydroxyl or acetyl groups at appropriate positions on the trichothecene nucleus and the structure and position of the side-chain. They are produced on many different grains like wheat, oats or maize by various Fusarium species such as F. graminearum, F. sporotrichioides, F. poae and F. equiseti. Some molds that produce trichothecene mycotoxins, such as Stachybotrys chartarum, can grow in damp indoor environments and may contribute to health problems among building occupants. (L1948) |
| FRCD ID | F04965 |
| CAS Number | 6379-69-7 |
| PubChem CID | 6436600 |
| Formula | C19H24O5 |
| IUPAC Name | None |
| InChI Key | LJWZOKOFCBPNAG-AWAILGSRSA-N |
| InChI | InChI=1S/C19H24O5/c1-5-6-16(21)24-14-8-15-19(10-22-19)18(14,4)17(3)9-12(20)11(2)7-13(17)23-15/h5-7,13-15H,8-10H2,1-4H3/b6-5-/t13-,14-,15-,17+,18?,19?/m1/s1 |
| Canonical SMILES | CC=CC(=O)OC1CC2C3(C1(C4(CC(=O)C(=CC4O2)C)C)C)CO3 |
| Isomeric SMILES | C/C=C\C(=O)O[C@@H]1C[C@@H]2C3(C1([C@]4(CC(=O)C(=C[C@H]4O2)C)C)C)CO3 |
| Synonyms |
12,13-Epoxy-4-hydroxytrichothec-9-en-8-one crotonate
CCRIS 6650
NSC 92492
12,13-Epoxy-4-((1-oxo-2-butenyl)oxy)trichothec-9-en-8-one
Trichothec-9-en-8-one, 12,13-epoxy-4-hydroxy-, crotonate
Trichothec-9-en-8-one, 12,13-epoxy-4-((1-oxo-2-butenyl)oxy)-, (4beta)-
LS-157039
|
| Classifies |
Fungal Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Lipids and lipid-like molecules |
| Class | Prenol lipids |
| Subclass | Sesquiterpenoids |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Trichothecenes |
| Alternative Parents | |
| Molecular Framework | Aliphatic heteropolycyclic compounds |
| Substituents | Trichothecene skeleton - Fatty acid ester - Oxepane - Cyclohexenone - Oxane - Fatty acyl - Alpha,beta-unsaturated carboxylic ester - Enoate ester - Carboxylic acid ester - Cyclic ketone - Ketone - Oxacycle - Carboxylic acid derivative - Organoheterocyclic compound - Dialkyl ether - Oxirane - Ether - Monocarboxylic acid or derivatives - Organic oxygen compound - Hydrocarbon derivative - Carbonyl group - Organooxygen compound - Organic oxide - Aliphatic heteropolycyclic compound |
| Description | This compound belongs to the class of organic compounds known as trichothecenes. These are sesquiterpene mycotoxins structurally characterized by the presence of an epoxide ring and a benzopyran derivative with a variant number of hydroxyl, acetyl, or other substituents. The most important structural features causing the biological activities of trichothecenes are the 12,13-epoxy ring, the presence of hydroxyl or acetyl groups at appropriate positions on the trichothecene nucleus and the structure and position of the side-chain. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 332.396 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 3 |
| Complexity | 679 |
| Monoisotopic Mass | 332.162 |
| Exact Mass | 332.162 |
| XLogP | 1.9 |
| Formal Charge | 0 |
| Heavy Atom Count | 24 |
| Defined Atom Stereocenter Count | 4 |
| Undefined Atom Stereocenter Count | 2 |
| Defined Bond Stereocenter Count | 1 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.8801 |
| Human Intestinal Absorption | HIA+ | 0.9833 |
| Caco-2 Permeability | Caco2- | 0.5319 |
| P-glycoprotein Substrate | Substrate | 0.7213 |
| P-glycoprotein Inhibitor | Inhibitor | 0.9388 |
| Non-inhibitor | 0.6270 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.8060 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.7180 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8720 |
| CYP450 2D6 Substrate | Non-substrate | 0.8584 |
| CYP450 3A4 Substrate | Substrate | 0.7101 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.7810 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.9004 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9530 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.8918 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.7777 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.8667 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9888 |
| Non-inhibitor | 0.7807 | |
| AMES Toxicity | Non AMES toxic | 0.9132 |
| Carcinogens | Non-carcinogens | 0.9284 |
| Fish Toxicity | High FHMT | 0.9767 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9908 |
| Honey Bee Toxicity | High HBT | 0.8662 |
| Biodegradation | Not ready biodegradable | 0.9904 |
| Acute Oral Toxicity | IV | 0.3962 |
| Carcinogenicity (Three-class) | Non-required | 0.6386 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -4.8074 | LogS |
| Caco-2 Permeability | 1.0108 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 3.0326 | LD50, mol/kg |
| Fish Toxicity | -0.1480 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.9251 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| A Lipid Transfer Protein Increases the Glutathione Content and Enhances Arabidopsis Resistance to a Trichothecene Mycotoxin. | PLoS One | 2015 | 26057253 |
| Elimination of damaged mitochondria through mitophagy reduces mitochondrial oxidative stress and increases tolerance to trichothecenes. | Proc Natl Acad Sci U S A | 2014 Aug 12 | 25071194 |
| Trichothecin induces apoptosis of HepG2 cells via caspase-9 mediated activation of the mitochondrial death pathway. | Toxicon | 2012 Jan | 22118979 |
| [Study of specificity of fungistatic effect of trichothecene mycotoxins]. | Mikrobiol Z | 2009 Mar-Apr | 19938595 |
| A genome-wide screen in Saccharomyces cerevisiae reveals a critical role for the mitochondria in the toxicity of a trichothecene mycotoxin. | Proc Natl Acad Sci U S A | 2009 Dec 22 | 20007368 |
| Natural product chemistry meets genetics: when is a genotype a chemotype? | J Agric Food Chem | 2008 Sep 10 | 18690691 |
| [Significance of toxic metabolites of the fungus Trichothecium roseum Link ex Fr. for viticulture]. | Z Lebensm Unters Forsch | 1989 Jun | 2763715 |
| Sulfhydryl groups and food safety. | Adv Exp Med Biol | 1984 | 6437164 |
Targets
- General Function:
- Structural constituent of ribosome
- Gene Name:
- MRPS5
- Uniprot ID:
- P82675
- Molecular Weight:
- 48006.135 Da
- Mechanism of Action:
- Trichothecenes move freely across the plasma membrane and bind specifically to ribosomes with high-affinity. Specifically, they interfere with the active site of peptidyl transferase at the 3'-end of large 28S ribosomal RNA and inhibit the initiation, elongation or termination step of protein synthesis, as well as cause polyribosomal disaggregation. Trichothecenes are cytotoxic because protein synthesis is an essential function in all tissues. Additionally, binding to ribosomes is thought to activate proteins in downstream signalling events related to immune response and apoptosis, such as mitogen-activated protein kinases. This is known as ribotoxic stress response.
References
- Pestka JJ: Mechanisms of deoxynivalenol-induced gene expression and apoptosis. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2008 Sep;25(9):1128-40. [19238623 ]
- General Function:
- Temperature-gated cation channel activity
- Specific Function:
- Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function (PubMed:25389312, PubMed:25855297). Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, cinnamaldehyde, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes (PubMed:25389312, PubMed:20547126). Is also activated by menthol (in vitro)(PubMed:25389312). Acts also as a ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana (PubMed:25389312). May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system (By similarity).
- Gene Name:
- TRPA1
- Uniprot ID:
- O75762
- Molecular Weight:
- 127499.88 Da
References
- Nilius B, Prenen J, Owsianik G: Irritating channels: the case of TRPA1. J Physiol. 2011 Apr 1;589(Pt 7):1543-9. doi: 10.1113/jphysiol.2010.200717. Epub 2010 Nov 15. [21078588 ]