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Record Information
Version2.0
Creation Date2014-08-29 05:30:44 UTC
Update Date2014-12-24 20:26:40 UTC
Accession NumberT3D4138
Identification
Common NameAnatoxin-a(s)
ClassSmall Molecule
DescriptionAnatoxin-a(s) is a natural organophosphate found in Anabaena flos-aquae. It irreversibly inhibits acetylcholinesterase (AChE), similar to organophosphorous and carbamate insecticides and some chemical warfare agents. When AChE is inhibited, the neurotransmitter acetylcholine is no longer hydrolyzed in the synapse, the postsynaptic membrane cannot be repolarized, and nerve influx is blocked. Anatoxin-a(s) is highly toxic for mammals when the toxigenic cyanobacteria produce mass populations in drinking water (1).
Compound Type
  • Amide
  • Amine
  • Bacterial Toxin
  • Ester
  • Insecticide
  • Natural Compound
  • Organic Compound
  • Pesticide
Chemical Structure
Thumb
Synonyms
Synonym
Anatoxin-a(S)
Phosphoric acid, mono[(5S)-2-amino-5-[(dimethylamino)methyl]-4,5-dihydro-1H-imidazol-1-yl] monomethyl ester
Chemical FormulaC7H17N4O4P
Average Molecular Mass252.208 g/mol
Monoisotopic Mass252.099 g/mol
CAS Registry Number103170-78-1
IUPAC Name{[(5R)-5-[(dimethylamino)methyl]-2-iminoimidazolidin-1-yl]oxy}(methoxy)phosphinic acid
Traditional Name[(5R)-5-[(dimethylamino)methyl]-2-iminoimidazolidin-1-yl]oxy(methoxy)phosphinic acid
SMILES[H][C@]1(CN(C)C)CNC(=N)N1OP(O)(=O)OC
InChI IdentifierInChI=1S/C7H17N4O4P/c1-10(2)5-6-4-9-7(8)11(6)15-16(12,13)14-3/h6H,4-5H2,1-3H3,(H2,8,9)(H,12,13)/t6-/m1/s1
InChI KeyInChIKey=FYXHGVMFJYHPFX-ZCFIWIBFSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as monoalkyl phosphates. These are organic compounds containing a phosphate group that is linked to exactly one alkyl chain.
KingdomChemical entities
Super ClassOrganic compounds
ClassOrganic acids and derivatives
Sub ClassOrganic phosphoric acids and derivatives
Direct ParentMonoalkyl phosphates
Alternative Parents
Substituents
  • Monoalkyl phosphate
  • 2-imidazoline
  • Guanidine
  • Tertiary amine
  • Tertiary aliphatic amine
  • Carboximidamide
  • Propargyl-type 1,3-dipolar organic compound
  • Organic 1,3-dipolar compound
  • Organoheterocyclic compound
  • Azacycle
  • Organic oxide
  • Organopnictogen compound
  • Organooxygen compound
  • Hydrocarbon derivative
  • Amine
  • Organic nitrogen compound
  • Organic oxygen compound
  • Organonitrogen compound
  • Aliphatic heteromonocyclic compound
Molecular FrameworkAliphatic heteromonocyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue Locations
  • Nerve Synapse
Pathways
NameSMPDB LinkKEGG Link
Metabolic PathwaysNot AvailableNot Available
ApoptosisNot Availablemap04210
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 Solubility10.0 mg/mLALOGPS
logP-1.3ALOGPS
logP-1.6ChemAxon
logS-1.4ALOGPS
pKa (Strongest Acidic)0.69ChemAxon
pKa (Strongest Basic)9.11ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area98.12 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity68.25 m3·mol-1ChemAxon
Polarizability22.81 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udi-0190000000-2f62c669c5a8d6a9c98eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0006-8980000000-fd5d4af83dab8fb637f3View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000w-9300000000-20b42a9d9ea66661a931View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-1390000000-5d0bc9c8d70da53b1419View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000i-7930000000-703b9141382ab9535479View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-002f-9310000000-c499e6b5c8752a091b17View in MoNA
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityAnatoxin-a(s) is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen.
MetabolismMetabolism of organophosphates occurs principally by oxidation, by hydrolysis via esterases and by reaction with glutathione. Demethylation and glucuronidation may also occur. Oxidation of organophosphorus pesticides may result in moderately toxic products. In general, phosphorothioates are not directly toxic but require oxidative metabolism to the proximal toxin. The glutathione transferase reactions produce products that are, in most cases, of low toxicity. Paraoxonase (PON1) is a key enzyme in the metabolism of organophosphates. PON1 can inactivate some organophosphates through hydrolysis. PON1 hydrolyzes the active metabolites in several organophosphates insecticides as well as, nerve agents such as soman, sarin, and VX. The presence of PON1 polymorphisms causes there to be different enzyme levels and catalytic efficiency of this esterase, which in turn suggests that different individuals may be more susceptible to the toxic effect of organophosphate exposure.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesNot Available
Minimum Risk LevelNot Available
Health EffectsAcute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergic syndrome, intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP), and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes result after acute and chronic exposure to OP pesticides.
SymptomsSymptoms of low dose exposure include excessive salivation and eye-watering. Acute dose symptoms include severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Hypertension, hypoglycemia, anxiety, headache, tremor and ataxia may also result.
TreatmentIf the compound has been ingested, rapid gastric lavage should be performed using 5% sodium bicarbonate. For skin contact, the skin should be washed with soap and water. If the compound has entered the eyes, they should be washed with large quantities of isotonic saline or water. In serious cases, atropine and/or pralidoxime should be administered. Anti-cholinergic drugs work to counteract the effects of excess acetylcholine and reactivate AChE. Atropine can be used as an antidote in conjunction with pralidoxime or other pyridinium oximes (such as trimedoxime or obidoxime), though the use of '-oximes' has been found to be of no benefit, or possibly harmful, in at least two meta-analyses. Atropine is a muscarinic antagonist, and thus blocks the action of acetylcholine peripherally.
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID114989
ChEMBL IDNot Available
ChemSpider ID102921
KEGG IDC19998
UniProt IDNot Available
OMIM ID
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
MSDST3D4138.pdf
General References
  1. Devic E, Li D, Dauta A, Henriksen P, Codd GA, Marty JL, Fournier D: Detection of anatoxin-a(s) in environmental samples of cyanobacteria by using a biosensor with engineered acetylcholinesterases. Appl Environ Microbiol. 2002 Aug;68(8):4102-6. [12147513 ]
  2. Hyde EG, Carmichael WW: Anatoxin-a(s), a naturally occurring organophosphate, is an irreversible active site-directed inhibitor of acetylcholinesterase (EC 3.1.1.7). J Biochem Toxicol. 1991 Fall;6(3):195-201. [1770503 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available