Anatoxin a (T3D4124)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (1)XML
Targets (1)
Record Information
Version2.0
Creation Date2014-08-29 05:21:37 UTC
Update Date2014-12-24 20:26:39 UTC
Accession NumberT3D4124
Identification
Common NameAnatoxin a
ClassSmall Molecule
DescriptionAnatoxin-a, also known as Very Fast Death Factor, is a secondary, bicyclic amine alkaloid and cyanotoxin with acute neurotoxicity. It was first discovered in the early 1960s in Canada, and was isolated in 1972. The toxin is produced by seven different genera of cyanobacteria and has been reported in North America, Europe, Africa, Asia, and New Zealand. Symptoms of anatoxin exposure include loss of coordination, muscular fasciculations, convulsions and death by respiratory paralysis. Its mode of action is through the nicotinic acetylcholine receptor (nAchR) where it acts as an agonist of acetylcholine. As such, anatoxin-a has been used for medicinal purposes to investigate diseases characterized by low acetylcholine levels. Due to its high toxicity and potential presence in drinking water, anatoxin-a poses a threat to humans and animals. While methods for detection and water treatment exist, scientists have called for more research to improve reliability and efficacy. Anatoxin-a is not to be confused with anatoxin-a(S), another potent cyanotoxin that has a similar mechanism of action to that of anatoxin-a and is produced by many of the same cyanobacteria genera, but is structurally unrelated.
Compound Type
  • Amine
  • Bacterial Toxin
  • Ester
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
SynonymsNot Available
Chemical FormulaC10H15NO
Average Molecular Mass165.232 g/mol
Monoisotopic Mass165.115 g/mol
CAS Registry Number64285-06-9
IUPAC Name1-{9-azabicyclo[4.2.1]non-2-en-2-yl}ethan-1-one
Traditional Nameanatoxin-a
SMILESCC(=O)C1=CCCC2CCC1N2
InChI IdentifierInChI=1/C10H15NO/c1-7(12)9-4-2-3-8-5-6-10(9)11-8/h4,8,10-11H,2-3,5-6H2,1H3
InChI KeyInChIKey=SGNXVBOIDPPRJJ-UHFFFAOYNA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as anatoxins. These are organic compounds containing or derived from anatoxin, homoanatoxin or other analogues. Anatoxins constitute a class of potent neurotoxic alkaloids.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassAnatoxins
Sub ClassNot Available
Direct ParentAnatoxins
Alternative Parents
Substituents
  • Anatoxin skeleton
  • Azepine
  • Beta-aminoketone
  • Pyrrolidine
  • Ketone
  • Secondary aliphatic amine
  • Secondary amine
  • Organoheterocyclic compound
  • Azacycle
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxide
  • Carbonyl group
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Amine
  • Organic nitrogen compound
  • Organic oxygen compound
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Plasma Membrane
  • Sarcoplasmic Reticulum
Biofluid LocationsNot Available
Tissue Locations
  • Nerve Synapse
Pathways
NameSMPDB LinkKEGG Link
ApoptosisNot Availablemap04210
Rna polymeraseNot Availablemap03020
Metabolic PathwaysNot AvailableNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility5.57 g/LALOGPS
logP1.25ALOGPS
logP1.19ChemAxon
logS-1.5ALOGPS
pKa (Strongest Acidic)19.12ChemAxon
pKa (Strongest Basic)10.21ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area29.1 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity48.83 m³·mol⁻¹ChemAxon
Polarizability18.59 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-007c-5900000000-ba20b4a810e4d42d829b2021-09-24View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-0900000000-102ee8cf61f9a3fca40f2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014i-1900000000-62ceaf7d188b3e837a0a2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0frx-9100000000-86534e8472925e41161d2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-0900000000-61d9204215a77bd1ba8d2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03k9-0900000000-0441fd550dfe2b4045ad2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00dl-7900000000-d66fc910a434d2965dae2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-0900000000-a8baa4b5218fe504eb782021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014i-1900000000-1056846b3b1bb9f819302021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00di-4900000000-3a6f2ccf799ae8ef31632021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-0900000000-5a67776f4d9f6897ce742021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03di-0900000000-86ab77a5296b6cbb848b2021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-03kd-4900000000-29dfc9ff3d3d7c9d9b9e2021-10-12View Spectrum
1D NMR1H NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR13C NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR1H NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR13C NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR1H NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR13C NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR1H NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR13C NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR13C NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR13C NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR1H NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR13C NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR13C NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR1H NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR13C NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
1D NMR1H NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-10-13View Spectrum
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityAnatoxin-a is an agonist of both neuronal α4β2 and α4 nicotinic acetylcholine receptors present in the CNS as well as the α12βγδ muscle-type nAchRs that are present at the neuromuscular junction. Anatoxin-a has an affinity for these receptors that is about 20 times greater than that of acetylcholine. Anatoxin-a also shows much less potency in the CNS than in neuromuscular junctions. In hippocampal and brain stem neurons, a 5 to 10 times greater concentration of anatoxin-a was necessary to activate nAchRs than what was required in the PNS. Anatoxin-a binding is irreversible, and the anatoxin-a nAchR complex cannot be broken down by acetylcholinesterase. Thus, the nAchR is temporarily locked open and after a period of time becomes desensitized. In this desensitized state the nAchRs no longer let cations pass through, which ultimately leads to a blockage of neuromuscular transmission.
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesAnatoxin-a, also known as Very Fast Death Factor, is a secondary, bicyclic amine alkaloid and cyanotoxin with acute neurotoxicity. It was first discovered in the early 1960s in Canada, and was isolated in 1972. The toxin is produced by seven different genera of cyanobacteria and has been reported in North America, Europe, Africa, Asia, and New Zealand. Symptoms of anatoxin exposure include loss of coordination, muscular fasciculations, convulsions and death by respiratory paralysis. As such, anatoxin-a has been used for medicinal purposes to investigate diseases characterized by low acetylcholine levels. Due to its high toxicity and potential presence in drinking water, anatoxin-a poses a threat to humans and animals. While methods for detection and water treatment exist, scientists have called for more research to improve reliability and efficacy. Anatoxin-a is not to be confused with anatoxin-a(S), another potent cyanotoxin that has a similar mechanism of action to that of anatoxin-a and is produced by many of the same cyanobacteria genera, but is structurally unrelated. (Wikipedia)
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID431734
ChEMBL IDCHEMBL25619
ChemSpider ID381822
KEGG IDC10841
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkAnatoxin-a
References
Synthesis ReferenceNot Available
MSDST3D4124.pdf
General References
  1. Araoz R, Molgo J, Tandeau de Marsac N: Neurotoxic cyanobacterial toxins. Toxicon. 2010 Oct;56(5):813-28. doi: 10.1016/j.toxicon.2009.07.036. Epub 2009 Aug 4. [19660486 ]
  2. Osswald J, Rellan S, Gago A, Vasconcelos V: Toxicology and detection methods of the alkaloid neurotoxin produced by cyanobacteria, anatoxin-a. Environ Int. 2007 Nov;33(8):1070-89. Epub 2007 Jul 30. [17673293 ]
  3. Botana L.M, James K, Crowley J, Duphard J, Lehane M, Furey A. Phycotoxins: Chemistry and Biochemistry. Blackwell Publishing; 2007. DOI: 10.1002/9780470277874.ch8 [ISBN: 9780813827001]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Neuronal acetylcholine receptor subunit alpha-4
General Function:
Ligand-gated ion channel activity
Specific Function:
After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane permeable to sodium ions.
Gene Name:
CHRNA4
Uniprot ID:
P43681
Molecular Weight:
69956.47 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory0.0011 uMNot AvailableBindingDB 50023330
References
  1. Mazurov AA, Miao L, Bhatti BS, Strachan JP, Akireddy S, Murthy S, Kombo D, Xiao YD, Hammond P, Zhang J, Hauser TA, Jordan KG, Miller CH, Speake JD, Gatto GJ, Yohannes D: Discovery of 3-(5-chloro-2-furoyl)-3,7-diazabicyclo[3.3.0]octane (TC-6683, AZD1446), a novel highly selective alpha4beta2 nicotinic acetylcholine receptor agonist for the treatment of cognitive disorders. J Med Chem. 2012 Nov 8;55(21):9181-94. doi: 10.1021/jm3006542. Epub 2012 Jul 27. [22793665 ]