Territrem C

Basic Info

Common NameTerritrem C(F04992)
2D Structure
Description

Territrem C 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 IDF04992
CAS Number89020-33-7
PubChem CID160306
FormulaC28H32O9
IUPAC Name

None

InChI Key

FTTNXWIFPFEOQT-JUDWXZBOSA-N

InChI

InChI=1S/C28H32O9/c1-24(2)8-7-21(29)26(4)27(24,32)10-9-25(3)28(26,33)14-16-18(37-25)13-17(36-23(16)31)15-11-19(34-5)22(30)20(12-15)35-6/h7-8,11-13,30,32-33H,9-10,14H2,1-6H3/t25-,26+,27-,28-/m1/s1

Canonical SMILES

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

Isomeric SMILES

C[C@@]12CC[C@@]3([C@@]([C@]1(CC4=C(O2)C=C(OC4=O)C5=CC(=C(C(=C5)OC)O)OC)O)(C(=O)C=CC3(C)C)C)O

Synonyms
        
            Territrem C
        
            89020-33-7
        
            CHEMBL3632858
        
            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-(4-hydroxy-3,5-dimethoxyphenyl)-4,4,6a,12b-tetramethyl-, (4aR-(4a-alpha,6a-beta,12a-alpha,12b-beta))-
        
            AC1L4NE7
        
            CTK5G2449
        
            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-(4-hydroxy-3,5-dimethoxyphenyl)-4,4,6a,12b-tetramethyl-,(4aR,6aR,12aS,12bS)-
        
            BDBM50130204
        
            LS-95587
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 - Methoxyphenol - Naphthalene - Dimethoxybenzene - M-dimethoxybenzene - Phenoxy compound - Anisole - Phenol ether - Methoxybenzene - Alkyl aryl ether - Cyclohexenone - Phenol - Pyranone - Pyran - Benzenoid - Monocyclic benzene moiety - Vinylogous ester - Heteroaromatic compound - Tertiary alcohol - Cyclic alcohol - Ketone - Lactone - Oxacycle - Ether - 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 Weight512.555
Hydrogen Bond Donor Count3
Hydrogen Bond Acceptor Count9
Rotatable Bond Count3
Complexity1110
Monoisotopic Mass512.205
Exact Mass512.205
XLogP2.5
Formal Charge0
Heavy Atom Count37
Defined Atom Stereocenter Count4
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Isotope Atom Count0
Covalently-Bonded Unit Count1

ADMET

Model Result Probability
Absorption
Blood-Brain BarrierBBB-0.7308
Human Intestinal AbsorptionHIA+0.9110
Caco-2 PermeabilityCaco2-0.6692
P-glycoprotein SubstrateSubstrate0.8894
P-glycoprotein InhibitorNon-inhibitor0.5994
Inhibitor0.8658
Renal Organic Cation TransporterNon-inhibitor0.9261
Distribution
Subcellular localizationMitochondria0.6488
Metabolism
CYP450 2C9 SubstrateNon-substrate0.7768
CYP450 2D6 SubstrateNon-substrate0.8706
CYP450 3A4 SubstrateSubstrate0.7155
CYP450 1A2 InhibitorNon-inhibitor0.7188
CYP450 2C9 InhibitorNon-inhibitor0.8576
CYP450 2D6 InhibitorNon-inhibitor0.9201
CYP450 2C19 InhibitorNon-inhibitor0.8655
CYP450 3A4 InhibitorNon-inhibitor0.5487
CYP Inhibitory PromiscuityLow CYP Inhibitory Promiscuity0.9363
Excretion
Toxicity
Human Ether-a-go-go-Related Gene InhibitionWeak inhibitor0.9871
Non-inhibitor0.7114
AMES ToxicityNon AMES toxic0.8386
CarcinogensNon-carcinogens0.9410
Fish ToxicityHigh FHMT0.9976
Tetrahymena Pyriformis ToxicityHigh TPT0.9995
Honey Bee ToxicityHigh HBT0.6977
BiodegradationNot ready biodegradable0.9944
Acute Oral ToxicityI0.3643
Carcinogenicity (Three-class)Non-required0.5934
Model Value Unit
Absorption
Aqueous solubility-4.4758LogS
Caco-2 Permeability0.5711LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity3.5963LD50, mol/kg
Fish Toxicity0.8062pLC50, mg/L
Tetrahymena Pyriformis Toxicity1.5829pIGC50, ug/L

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 ]