T3DB: Aconitine

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation Targets (14)XML

Targets (14)

Record Information

Version

2.0

Creation Date

2009-07-23 18:26:06 UTC

Update Date

2014-12-24 20:25:57 UTC

Accession Number

T3D3078

Identification

Common Name

Aconitine

Class

Small Molecule

Description

Aconitine is a plant toxin found in species of wolfsbane (Aconitum genus). It is a neurotoxin previously used as an antipyretic and analgesic, and still has some limited application in herbal medicine. (1). The toxic effects of Aconitine have been tested in a variety of different test animals, including mammals (dog, cat, guinea pig, mouse, rat and rabbit), frogs and pigeons. Depending on the route of exposure, the observed toxic effects were: local anesthetic effect, diarrhea, convulsions, arrhythmias or death. According to a review of different reports of aconite poisoning in humans the following clinical features were observed: Neurological, Cardiovascular, Ventricular arrhythmias, Gastrointestinal.

Compound Type

Amine
Ester
Ether
Natural Compound
Organic Compound
Plant Toxin

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
(1‘±,3‘±,6‘±,14‘±,16beta)-8-(acetyloxy)-20-ethyl-3,13,15-trihydroxy-1,6,16-trimethoxy-4-(methoxymethyl)aconitan-14-yl benzoate
Aconitane
Aconitin cristallisat

Chemical Formula

C₃₄H₄₇NO₁₁

Average Molecular Mass

645.737 g/mol

Monoisotopic Mass

645.315 g/mol

CAS Registry Number

302-27-2

IUPAC Name

(1S,2R,3R,4R,5R,6S,7S,8R,9R,13R,14R,16S,17S,18R)-8-(acetyloxy)-11-ethyl-5,7,14-trihydroxy-6,16,18-trimethoxy-13-(methoxymethyl)-11-azahexacyclo[7.7.2.1²,⁵.0¹,¹⁰.0³,⁸.0¹³,¹⁷]nonadecan-4-yl benzoate

Traditional Name

aconitine

SMILES

[H][C@@]12C[C@@]3(O)[C@]([H])(OC(=O)C4=CC=CC=C4)[C@]1([H])[C@@](OC(C)=O)([C@@]1([H])[C@]([H])(OC)[C@@]4([H])[C@]22C1([H])N(CC)C[C@]4(COC)[C@]([H])(O)C[C@]2([H])OC)[C@@]([H])(O)[C@]3([H])OC

InChI Identifier

InChI=1S/C34H47NO11/c1-7-35-15-31(16-41-3)20(37)13-21(42-4)33-19-14-32(40)28(45-30(39)18-11-9-8-10-12-18)22(19)34(46-17(2)36,27(38)29(32)44-6)23(26(33)35)24(43-5)25(31)33/h8-12,19-29,37-38,40H,7,13-16H2,1-6H3/t19-,20?,21+,22-,23+,24+,25-,26?,27+,28-,29+,31+,32-,33+,34-/m1/s1

InChI Key

InChIKey=XFSBVAOIAHNAPC-BHMXGGQCSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as aconitane-type diterpenoid alkaloids. These are alkaloid diterpenoids with a structure based on the hexacyclic aconitane skeleton. These compounds have no oxygen functionality at the C7 atom.

Kingdom

Organic compounds

Super Class

Lipids and lipid-like molecules

Class

Prenol lipids

Sub Class

Diterpenoids

Direct Parent

Aconitane-type diterpenoid alkaloids

Alternative Parents

Substituents

Aconitane-type diterpenoid alkaloid
Quinolidine
Benzoate ester
Alkaloid or derivatives
Benzoic acid or derivatives
Benzoyl
Azepane
Benzenoid
Piperidine
Dicarboxylic acid or derivatives
Monocyclic benzene moiety
Tertiary alcohol
Cyclic alcohol
Tertiary aliphatic amine
Tertiary amine
Secondary alcohol
Carboxylic acid ester
Amino acid or derivatives
Azacycle
Organoheterocyclic compound
Polyol
Ether
Dialkyl ether
Carboxylic acid derivative
Organic nitrogen compound
Organic oxygen compound
Organopnictogen compound
Organic oxide
Hydrocarbon derivative
Organooxygen compound
Organonitrogen compound
Carbonyl group
Amine
Alcohol
Aromatic heteropolycyclic compound

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

Not Available

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Cell junction
Cytoplasm
Extracellular
Microsome
Mitochondrion
Nerve Fiber
Plasma Membrane
Sarcoplasmic Reticulum

Biofluid Locations

Not Available

Tissue Locations

Not Available

Pathways

Name	SMPDB Link	KEGG Link
Bacterial Chemotaxis	Not Available	Not Available
Antiarrhythmic Drugs	Not Available	Not Available
Rna polymerase	Not Available	map03020
Anticonvulsants	Not Available	Not Available
Apoptosis	Not Available	map04210

Applications

Not Available

Biological Roles

Not Available

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	204°C
Boiling Point	Not Available
Solubility	0.31 mg/mL at 25°C [SEIDELL,A (1941)]
LogP	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.71 g/L	ALOGPS
logP	1.68	ALOGPS
logP	-0.54	ChemAxon
logS	-3	ALOGPS
pKa (Strongest Acidic)	12.53	ChemAxon
pKa (Strongest Basic)	9.74	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	10	ChemAxon
Hydrogen Donor Count	3	ChemAxon
Polar Surface Area	153.45 Å²	ChemAxon
Rotatable Bond Count	11	ChemAxon
Refractivity	161.8 m³·mol⁻¹	ChemAxon
Polarizability	67.75 Å³	ChemAxon
Number of Rings	7	ChemAxon
Bioavailability	0	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	Yes	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-054k-0200069000-d5c43adf2d9e5a964f8f	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0a4i-1400095000-f69fe66a37b8742f9d88	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0a4i-3900330000-f75578a0c542f4c59099	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0006-3100039000-2583a09e7f0123c13d6e	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-056r-4200096000-b0486e36508050714f60	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-05i0-9400050000-88bb6a79c21e8a17f798	2016-08-03	View Spectrum

Toxicity Profile

Route of Exposure

Oral (ingestion) (2) ; dermal (2)

Mechanism of Toxicity

Aconitine opens voltage-gated sodium channed in the heart and other tissues. (1)

Metabolism

Not Available

Toxicity Values

LD50: 0.166 mg/kg (Intravenous, Mouse) (1) LD50: 0.328 mg/kg (Intraperitoneal, Mouse) (1) LD50: 1 mg/kg (Oral, Mouse) (1)

Lethal Dose

1.5 to 6 mg for an adult human. (1)

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Uses/Sources

Minimum Risk Level

Not Available

Health Effects

Aconitine may cause death from respiratory paralysis and cardiac arrest. (1)

Symptoms

Symptoms of acontine poisoning include paresthesia of the whole body, starting from the extremities, anesthesia, sweating and cooling of the body, nausea, and vomiting. Sometimes there is strong pain, accompanied by cramps, or diarrhea. (1)

Treatment

As there is no antidote to acontine, treatment is symptomatic and may include administering atropine, strychnine or barakol. (1)

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

Not Available

HMDB ID

Not Available

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

2430

BioCyc ID

Not Available

CTD ID

Not Available

Stitch ID

Aconitine

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Not Available

References

Synthesis Reference

Not Available

MSDS

T3D3078.pdf

General References

Wikipedia. Aconitine. Last Updated 11 July 2009. [Link]
Wikipedia. Phytotoxin. Last Updated 7 August 2009. [Link]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Targets

Target Details

1. Sodium channel protein type 1 subunit alpha

General Function:: Voltage-gated sodium channel activity
Specific Function:: Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
Gene Name:: SCN1A
Uniprot ID:: P35498
Molecular Weight:: 228969.49 Da

References

Target Details

2. Sodium channel protein type 10 subunit alpha

General Function:: Voltage-gated sodium channel activity
Specific Function:: Tetrodotoxin-resistant channel that mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which sodium ions may pass in accordance with their electrochemical gradient. Plays a role in neuropathic pain mechanisms.
Gene Name:: SCN10A
Uniprot ID:: Q9Y5Y9
Molecular Weight:: 220623.605 Da

References

Target Details

3. Sodium channel protein type 11 subunit alpha

General Function:: Voltage-gated sodium channel activity
Specific Function:: This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which sodium ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant sodium channel isoform. Also involved, with the contribution of the receptor tyrosine kinase NTRK2, in rapid BDNF-evoked neuronal depolarization.
Gene Name:: SCN11A
Uniprot ID:: Q9UI33
Molecular Weight:: 204919.66 Da

References

Target Details

4. Sodium channel protein type 2 subunit alpha

General Function:: Voltage-gated sodium channel activity
Specific Function:: Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
Gene Name:: SCN2A
Uniprot ID:: Q99250
Molecular Weight:: 227972.64 Da

References

Target Details

5. Sodium channel protein type 3 subunit alpha

General Function:: Voltage-gated sodium channel activity
Specific Function:: Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
Gene Name:: SCN3A
Uniprot ID:: Q9NY46
Molecular Weight:: 226291.905 Da

References

Target Details

6. Sodium channel protein type 4 subunit alpha

General Function:: Voltage-gated sodium channel activity
Specific Function:: This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. This sodium channel may be present in both denervated and innervated skeletal muscle.
Gene Name:: SCN4A
Uniprot ID:: P35499
Molecular Weight:: 208059.175 Da

References

Target Details

7. Sodium channel protein type 5 subunit alpha

General Function:: Voltage-gated sodium channel activity involved in sa node cell action potential
Specific Function:: This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential. Channel inactivation is regulated by intracellular calcium levels.
Gene Name:: SCN5A
Uniprot ID:: Q14524
Molecular Weight:: 226937.475 Da

References

Target Details

8. Sodium channel protein type 7 subunit alpha

General Function:: Voltage-gated sodium channel activity
Specific Function:: Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
Gene Name:: SCN7A
Uniprot ID:: Q01118
Molecular Weight:: 193491.605 Da

References

Target Details

9. Sodium channel protein type 8 subunit alpha

General Function:: Voltage-gated sodium channel activity
Specific Function:: Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. In macrophages and melanoma cells, isoform 5 may participate in the control of podosome and invadopodia formation.
Gene Name:: SCN8A
Uniprot ID:: Q9UQD0
Molecular Weight:: 225278.005 Da

References

Target Details

10. Sodium channel protein type 9 subunit alpha

General Function:: Voltage-gated sodium channel activity
Specific Function:: Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-sensitive Na(+) channel isoform. Plays a role in pain mechanisms, especially in the development of inflammatory pain (By similarity).
Gene Name:: SCN9A
Uniprot ID:: Q15858
Molecular Weight:: 226370.175 Da

References

Target Details

11. Sodium channel subunit beta-1

General Function:: Voltage-gated sodium channel activity involved in purkinje myocyte action potential
Specific Function:: Crucial in the assembly, expression, and functional modulation of the heterotrimeric complex of the sodium channel. The subunit beta-1 can modulate multiple alpha subunit isoforms from brain, skeletal muscle, and heart. Its association with neurofascin may target the sodium channels to the nodes of Ranvier of developing axons and retain these channels at the nodes in mature myelinated axons.Isoform 2: Cell adhesion molecule that plays a critical role in neuronal migration and pathfinding during brain development. Stimulates neurite outgrowth.
Gene Name:: SCN1B
Uniprot ID:: Q07699
Molecular Weight:: 24706.955 Da

References

Target Details

12. Sodium channel subunit beta-2

General Function:: Voltage-gated sodium channel activity involved in cardiac muscle cell action potential
Specific Function:: Crucial in the assembly, expression, and functional modulation of the heterotrimeric complex of the sodium channel. The subunit beta-2 causes an increase in the plasma membrane surface area and in its folding into microvilli. Interacts with TNR may play a crucial role in clustering and regulation of activity of sodium channels at nodes of Ranvier (By similarity).
Gene Name:: SCN2B
Uniprot ID:: O60939
Molecular Weight:: 24325.69 Da

References

Target Details

13. Sodium channel subunit beta-3

General Function:: Voltage-gated sodium channel activity involved in cardiac muscle cell action potential
Specific Function:: Modulates channel gating kinetics. Causes unique persistent sodium currents. Inactivates the sodium channel opening more slowly than the subunit beta-1. Its association with neurofascin may target the sodium channels to the nodes of Ranvier of developing axons and retain these channels at the nodes in mature myelinated axons (By similarity).
Gene Name:: SCN3B
Uniprot ID:: Q9NY72
Molecular Weight:: 24702.08 Da

References

Target Details

14. Sodium channel subunit beta-4

General Function:: Voltage-gated sodium channel activity involved in cardiac muscle cell action potential
Specific Function:: Modulates channel gating kinetics. Causes negative shifts in the voltage dependence of activation of certain alpha sodium channels, but does not affect the voltage dependence of inactivation. Modulates the suceptibility of the sodium channel to inhibition by toxic peptides from spider, scorpion, wasp and sea anemone venom.
Gene Name:: SCN4B
Uniprot ID:: Q8IWT1
Molecular Weight:: 24968.755 Da

References

Aconitine (T3D3078)

Structure for T3D3078: Aconitine

Targets

References

References

References

References

References

References

References

References

References

References

References

References

References

References