Territrem A

Basic Info

Common NameTerritrem A(F04991)
2D Structure
Description

Territrem 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. (A3028, A3029)

FRCD IDF04991
CAS Number70407-19-1
PubChem CID115079
FormulaC28H30O9
IUPAC Name

None

InChI Key

LCJHAHVVYAVVPA-UHFFFAOYSA-N

InChI

InChI=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

Canonical SMILES

CC1(C=CC(=O)C2(C1(CCC3(C2(CC4=C(O3)C=C(OC4=O)C5=CC6=C(C(=C5)OC)OCO6)O)C)O)C)C

Isomeric SMILES

CC1(C=CC(=O)C2(C1(CCC3(C2(CC4=C(O3)C=C(OC4=O)C5=CC6=C(C(=C5)OC)OCO6)O)C)O)C)C

Synonyms
        
            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))-
        
            Territrem A
        
            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)-
        
            70407-19-1
        
            AC1L3GHN
        
            AC1Q6ILL
        
            4a,12a-dihydroxy-9-(7-methoxy-1,3-benzodioxol-5-yl)-4,4,6a,12b-tetramethyl-4a,6,6a,12,12a,12b-hexahydro-4h,11h-benzo[f]pyrano[4,3-b]chromene-1,11(5h)-dione
        
            LS-95588
Classifies
                

                  
                    Fungal Toxin
Update DateNov 13, 2018 17:07

Chemical Taxonomy

KingdomOrganic compounds
SuperclassOrganoheterocyclic compounds
ClassNaphthopyrans
SubclassNot available
Intermediate Tree NodesNot available
Direct ParentNaphthopyrans
Alternative Parents
Molecular FrameworkAromatic heteropolycyclic compounds
SubstituentsNaphthopyran - Naphthalene - Benzodioxole - Anisole - Alkyl aryl ether - Cyclohexenone - Pyranone - Benzenoid - Pyran - Cyclic alcohol - Heteroaromatic compound - Vinylogous ester - Tertiary alcohol - Lactone - Ketone - Ether - Acetal - Oxacycle - Alcohol - Carbonyl group - Hydrocarbon derivative - Organooxygen compound - Organic oxygen compound - Organic oxide - Aromatic heteropolycyclic compound
DescriptionThis compound belongs to the class of organic compounds known as naphthopyrans. These are compounds containing a pyran ring fused to a naphthalene moiety. Furan is a 6 membered-ring non-aromatic ring with five carbon and one oxygen atoms. Naphthalene is a polycyclic aromatic hydrocarbon made up of two fused benzene rings.

Properties

Property NameProperty Value
Molecular Weight510.539
Hydrogen Bond Donor Count2
Hydrogen Bond Acceptor Count9
Rotatable Bond Count2
Complexity1150
Monoisotopic Mass510.189
Exact Mass510.189
XLogP2.7
Formal Charge0
Heavy Atom Count37
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count4
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Isotope Atom Count0
Covalently-Bonded Unit Count1

ADMET

Model Result Probability
Absorption
Blood-Brain BarrierBBB-0.8177
Human Intestinal AbsorptionHIA+0.9546
Caco-2 PermeabilityCaco2-0.6887
P-glycoprotein SubstrateSubstrate0.8584
P-glycoprotein InhibitorInhibitor0.5117
Inhibitor0.8795
Renal Organic Cation TransporterNon-inhibitor0.8741
Distribution
Subcellular localizationMitochondria0.7372
Metabolism
CYP450 2C9 SubstrateNon-substrate0.8178
CYP450 2D6 SubstrateNon-substrate0.8512
CYP450 3A4 SubstrateSubstrate0.7540
CYP450 1A2 InhibitorNon-inhibitor0.7923
CYP450 2C9 InhibitorNon-inhibitor0.7845
CYP450 2D6 InhibitorNon-inhibitor0.8997
CYP450 2C19 InhibitorNon-inhibitor0.8618
CYP450 3A4 InhibitorInhibitor0.8031
CYP Inhibitory PromiscuityLow CYP Inhibitory Promiscuity0.8183
Excretion
Toxicity
Human Ether-a-go-go-Related Gene InhibitionWeak inhibitor0.9874
Non-inhibitor0.6382
AMES ToxicityNon AMES toxic0.7500
CarcinogensNon-carcinogens0.9398
Fish ToxicityHigh FHMT0.9978
Tetrahymena Pyriformis ToxicityHigh TPT0.9996
Honey Bee ToxicityHigh HBT0.7157
BiodegradationNot ready biodegradable0.9781
Acute Oral ToxicityI0.5293
Carcinogenicity (Three-class)Non-required0.5163
Model Value Unit
Absorption
Aqueous solubility-4.2333LogS
Caco-2 Permeability0.7681LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity4.1831LD50, mol/kg
Fish Toxicity0.6466pLC50, mg/L
Tetrahymena Pyriformis Toxicity1.3800pIGC50, ug/L

References

TitleJournalDatePubmed ID
Aspergillus terreus and its toxic metabolites as a food contaminant in some Egyptian Bakery products and grains.Mycotoxin Res1998 Jun23605064
Solvent systems for improved isolation and separation of territrems A and B.Appl Environ Microbiol1982 Oct7149718

Targets

Target Details

Acetylcholinesterase

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:
Territrems 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.
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 ]