Record Information
Version2.0 (beta)
Creation Date2010-05-10 10:23:41 -0600
Update Date2014-09-03 07:54:15 -0600
Accession NumberT3D3746
Identification
Common NameTerritrem A
ClassSmall Molecule
DescriptionTerritrem A is a tremorgenic mycotoxin found in the fungus Aspergillus terreus, which has been know to contaminate rice crops. Tremorgenic mycotoxins affect central nervous system activity, with their defining characteristic being the tremors that they cause. Territrems induce this effect by inhibiting the enzyme acetylcholinesterase in peripheral nerve endings. (3, 4)
Compound Type
  • Organic Compound
  • Mycotoxin
Chemical Structure
Thumb
Synonyms
  1. 4H,11H-Naphtho(2,1-b)pyrano(3,4-e)pyran-1,11(5H)-dione, 4a,6,6a,12,12a,12b-hexahydro-4a,12a-dihydroxy-9-(7-methoxy-1,3-benzodioxo-5-yl)-4,4,6a,12b-tetramethyl-, (4aR,6aR,12aS,12bS)-
  2. 4H,11H-Naphtho(2,1-b)pyrano(3,4-e)pyran-1,11(5H)-dione, 4a,6,6a,12,12a,12b-hexahydro-4a,12a-dihydroxy-9-(7-methoxy-1,3-benzodioxo-5-yl)-4,4,6a,12b-tetramethyl-, (4aR-(4a-alpha,6a-beta,12a-alpha,12b-beta))-
Chemical FormulaC28H30O9
Average Molecular Weight510.5324 g/mol
CAS Registry Number70407-19-1
Monoisotopic Mass510.188982558 g/mol
IUPAC Name7a,11b-dihydroxy-3-(7-methoxy-2H-1,3-benzodioxol-5-yl)-5a,8,8,11a-tetramethyl-1,5a,6,7,7a,8,11,11a,11b,12-decahydro-2,5-dioxatetraphene-1,11-dione
Traditional IUPAC Name7a,11b-dihydroxy-3-(7-methoxy-2H-1,3-benzodioxol-5-yl)-5a,8,8,11a-tetramethyl-7,12-dihydro-6H-2,5-dioxatetraphene-1,11-dione
SMILESCOC1=CC(=CC2=C1OCO2)C1=CC2=C(CC3(O)C(C)(CCC4(O)C(C)(C)C=CC(=O)C34C)O2)C(=O)O1
InChI IdentifierInChI=1S/C28H30O9/c1-24(2)7-6-21(29)26(4)27(24,31)9-8-25(3)28(26,32)13-16-18(37-25)12-17(36-23(16)30)15-10-19(33-5)22-20(11-15)34-14-35-22/h6-7,10-12,31-32H,8-9,13-14H2,1-5H3
InChI KeyInChIKey=LCJHAHVVYAVVPA-UHFFFAOYSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassHeterocyclic Compounds
ClassNaphthopyrans
Sub ClassNot Available
Direct ParentNaphthopyrans
Alternative Parents
  • Naphthalenes
  • Benzodioxoles
  • Anisoles
  • Pyranones and Derivatives
  • Alkyl Aryl Ethers
  • Tertiary Alcohols
  • Vinylogous Esters
  • Cyclic Alcohols and Derivatives
  • Lactones
  • Acetals
  • Carbonyl Compounds
Substituents
  • naphthalene
  • anisole
  • alkyl aryl ether
  • benzodioxole
  • cyclic alcohol
  • acetal
  • alcohol
  • tertiary alcohol
  • lactone
  • pyran
  • pyranone
  • naphthopyran
  • Benzenoid
  • Ether
  • Organooxygen Compound
  • Aromatic Heteropolycyclic Compound
  • Vinylogous Ester
  • Carbonyl Group
External DescriptorsNot Available
Biological Properties
StatusDetected but not Quantified
OriginNot Available
Cellular LocationsNot Available
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Physical Properties
StateNot Available
AppearanceNot Available
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
water solubility2.53e-02 g/lALOGPS
logP2.3ALOGPS
logP2.44ChemAxon
logS-4.3ALOGPS
pKa (strongest acidic)5.5ChemAxon
pKa (strongest basic)-3.4ChemAxon
physiological charge0ChemAxon
hydrogen acceptor count8ChemAxon
hydrogen donor count2ChemAxon
polar surface area120.75ChemAxon
rotatable bond count2ChemAxon
refractivity133.18ChemAxon
polarizability53.42ChemAxon
Spectra
SpectraNot Available
Toxicity Profile
Route of ExposureOral, dermal, inhalation, and parenteral (contaminated drugs). (6)
Mechanism of ToxicityTerritrems act at the peripheral nerve endings as irreversible inhibitors of acetylcholinesterase. As acetylcholinesterase is needed to hydrolyze the neurotransmitter acetylcholine in cholinergic synapses, inhibition of this enzyme continually potentiates the acetylcholine-induced current of the neuron. It is thought that territrems inhibits acetylcholinesterase by becoming noncovalently trapped within the unique active-site gorge structure of the enzyme. (3, 4)
MetabolismThe biotransformation of territrems involves hydroxylation and 0-demethylation. Metabolism is performed by cytochrome P-450 monooxygenases in the liver, with CYP3A4 and CYP3A5 being the major enzymes used. (3, 5)
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)Not Available
Uses/SourcesTerritrem A is a tremorgenic mycotoxin found in the fungus Aspergillus terreus. (3)
Minimum Risk LevelNot Available
Health EffectsTremorgenic mycotoxins affect central nervous system activity. They cause a neurological disease of cattle known as "staggers syndrome". (2)
SymptomsTremorgenic mycotoxins affect central nervous system activity, inducing neurologic symptoms including mental confusion, paralysis, tremors, seizures, and death. They cause a neurological disease of cattle known as "staggers syndrome", which is characterized by muscle tremors and hyperexcitability. (2)
TreatmentTo control severe tremorscaused by tremorgenic mycotoxins, methocarbamol should be administered. Generalized seizures may be treated with diazepam followed by methocarbamol or a barbiturate such as pentobarbital sodium. Gastric lavage should be performed and activated charcoal administered to limit further absorption of toxins. (7)
Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID115079
ChEMBL IDNot Available
ChemSpider IDNot Available
KEGG IDNot Available
UniProt IDNot Available
OMIM IDNot Available
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDSNot Available
General References
  1. Valdes JJ, Cameron JE, Cole RJ: Aflatrem: a tremorgenic mycotoxin with acute neurotoxic effects. Environ Health Perspect. 1985 Oct;62:459-63. [2867895 ]
  2. Selala MI, Daelemans F, Schepens PJ: Fungal tremorgens: the mechanism of action of single nitrogen containing toxins--a hypothesis. Drug Chem Toxicol. 1989 Sep-Dec;12(3-4):237-57. [2698801 ]
  3. Ling KH, Chiou CM, Tseng YL: Biotransformation of territrems by S9 fraction from rat liver. Drug Metab Dispos. 1991 May-Jun;19(3):587-95. [1680623 ]
  4. Chen JW, Luo YL, Hwang MJ, Peng FC, Ling KH: Territrem B, a tremorgenic mycotoxin that inhibits acetylcholinesterase with a noncovalent yet irreversible binding mechanism. J Biol Chem. 1999 Dec 3;274(49):34916-23. [10574966 ]
  5. Peng FC, Chang CC, Yang CY, Edwards RJ, Doehmer J: Territrems B and C metabolism in human liver microsomes: major role of CYP3A4 and CYP3A5. Toxicology. 2006 Feb 1;218(2-3):172-85. Epub 2005 Dec 5. [16337070 ]
  6. Peraica M, Domijan AM: Contamination of food with mycotoxins and human health. Arh Hig Rada Toksikol. 2001 Mar;52(1):23-35. [11370295 ]
  7. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. JAMA. 1991 Jun 26;265(24):3255-64. [2046107 ]
  8. Schell MM. Tremorgenic mycotoxin intoxication. Veterinary Medicine. 2000.
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General function:
Lipid transport and metabolism
Specific function:
Rapidly hydrolyzes choline released into the synapse
Gene Name:
ACHE
Uniprot ID:
P22303
Molecular weight:
67797.0
References
  1. Ling KH, Chiou CM, Tseng YL: Biotransformation of territrems by S9 fraction from rat liver. Drug Metab Dispos. 1991 May-Jun;19(3):587-95. [1680623 ]
  2. Chen JW, Luo YL, Hwang MJ, Peng FC, Ling KH: Territrem B, a tremorgenic mycotoxin that inhibits acetylcholinesterase with a noncovalent yet irreversible binding mechanism. J Biol Chem. 1999 Dec 3;274(49):34916-23. [10574966 ]