Aconitine
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Basic Info
| Common Name | Aconitine(F04793) |
| 2D Structure | |
| 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. (L1235). 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. |
| FRCD ID | F04793 |
| CAS Number | 302-27-2 |
| PubChem CID | 245005 |
| Formula | C34H47NO11 |
| IUPAC Name | None |
| InChI Key | XFSBVAOIAHNAPC-XTHSEXKGSA-N |
| InChI | 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 |
| Canonical SMILES | CCN1CC2(C(CC(C34C2C(C(C31)C5(C6C4CC(C6OC(=O)C7=CC=CC=C7)(C(C5O)OC)O)OC(=O)C)OC)OC)O)COC |
| Isomeric SMILES | CCN1C[C@@]2([C@@H](C[C@@H]([C@@]34[C@@H]2[C@H]([C@@H](C31)[C@@]5([C@@H]6[C@H]4C[C@@]([C@@H]6OC(=O)C7=CC=CC=C7)([C@H]([C@@H]5O)OC)O)OC(=O)C)OC)OC)O)COC |
| Synonyms |
16-Ethyl-1alpha,6alpha,19beta-trimethoxy-4-(methoxymethyl)-aconitane-3alpha,8,10alpha,11,18alpha-pentol, 8-acetate 10-benzoate
aconitine
302-27-2
CHEBI:2430
Acetylbenzoylaconine
NSC56464
20-ethyl-3alpha,13,15alpha-trihydroxy-1alpha,6alpha,16beta-trimethoxy-4-(methoxymethyl)aconitane-8,14alpha-diyl 8-acetate 14-benzoate
NCGC00163146-01
CAS-302-27-2
D0A1MW
|
| Classifies |
Plant Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Lipids and lipid-like molecules |
| Class | Prenol lipids |
| Subclass | Diterpenoids |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Aconitane-type diterpenoid alkaloids |
| Alternative Parents |
|
| Molecular Framework | Aromatic heteropolycyclic compounds |
| Substituents | Aconitane-type diterpenoid alkaloid - Benzoate ester - Quinolidine - Benzoic acid or derivatives - Alkaloid or derivatives - Benzoyl - Azepane - Monocyclic benzene moiety - Dicarboxylic acid or derivatives - Piperidine - Benzenoid - Cyclic alcohol - Tertiary alcohol - Tertiary aliphatic amine - Secondary alcohol - Tertiary amine - Amino acid or derivatives - Carboxylic acid ester - Polyol - Organoheterocyclic compound - Carboxylic acid derivative - Azacycle - Dialkyl ether - Ether - Organopnictogen compound - Carbonyl group - Alcohol - Organic oxygen compound - Organic nitrogen compound - Organooxygen compound - Hydrocarbon derivative - Organic oxide - Amine - Organonitrogen compound - Aromatic heteropolycyclic compound |
| Description | This compound 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. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 645.746 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 12 |
| Rotatable Bond Count | 11 |
| Complexity | 1210 |
| Monoisotopic Mass | 645.315 |
| Exact Mass | 645.315 |
| XLogP | 0.3 |
| Formal Charge | 0 |
| Heavy Atom Count | 46 |
| Defined Atom Stereocenter Count | 14 |
| Undefined Atom Stereocenter Count | 1 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.6361 |
| Human Intestinal Absorption | HIA+ | 0.7516 |
| Caco-2 Permeability | Caco2- | 0.6324 |
| P-glycoprotein Substrate | Substrate | 0.8997 |
| P-glycoprotein Inhibitor | Inhibitor | 0.8807 |
| Non-inhibitor | 0.6706 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.7862 |
| Distribution | ||
| Subcellular localization | Lysosome | 0.5905 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8465 |
| CYP450 2D6 Substrate | Non-substrate | 0.8193 |
| CYP450 3A4 Substrate | Substrate | 0.6937 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.9045 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.9071 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9231 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.9025 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.8309 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.9299 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9856 |
| Inhibitor | 0.5452 | |
| AMES Toxicity | Non AMES toxic | 0.6588 |
| Carcinogens | Non-carcinogens | 0.9380 |
| Fish Toxicity | High FHMT | 0.9843 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9871 |
| Honey Bee Toxicity | High HBT | 0.5202 |
| Biodegradation | Not ready biodegradable | 0.9947 |
| Acute Oral Toxicity | I | 0.7618 |
| Carcinogenicity (Three-class) | Non-required | 0.5722 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -2.8209 | LogS |
| Caco-2 Permeability | 0.5125 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 4.7273 | LD50, mol/kg |
| Fish Toxicity | 1.3817 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.6091 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| C19-Norditerpenoid Alkaloids from <i>Aconitum szechenyianum</i>. | Molecules | 2018 May 8 | 29738430 |
| r-bPiDI, an α6β2* Nicotinic Receptor Antagonist, Decreases Nicotine-Evoked Dopamine Release and Nicotine Reinforcement. | Neurochem Res | 2015 Oct | 26227997 |
| A method for analysis of wilfordmine in human plasma by liquid chromatography coupled with ion trap mass spectrometry. | J Chromatogr Sci | 2015 Jan | 24895446 |
| Encapsulation of Aconitine in Self-Assembled Licorice Protein Nanoparticles Reduces the Toxicity In Vivo. | Nanoscale Res Lett | 2015 Dec | 26586149 |
| The influences of aconitine, an active/toxic alkaloid from aconitum, on the oral pharmacokinetics of CYP3A probe drug buspirone in rats. | Drug Metab Lett | 2014 | 25434398 |
| Development and assessment of a complete-detoxication strategy for Fuzi (lateral root of Aconitum carmichaeli) and its application in rheumatoid arthritis therapy. | J Ethnopharmacol | 2013 Mar 27 | 23376046 |
| Transcellular transport of aconitine across human intestinal Caco-2 cells. | Food Chem Toxicol | 2013 Jul | 23562926 |
| The exposure of highly toxic aconitine does not significantly impact the activity and expression of cytochrome P450 3A in rats determined by a novel ultra performance liquid chromatography-tandem mass spectrometric method of a specific probe buspirone. | Food Chem Toxicol | 2013 Jan | 23085095 |
| [Aconitine analogues in wild Aconitum plants: contents toxicity to mice and decrease by boiling]. | Shokuhin Eiseigaku Zasshi | 2013 | 24190290 |
| Screening of plant toxins in food, feed and botanicals using full-scan high-resolution (Orbitrap) mass spectrometry. | Food Addit Contam Part A Chem Anal Control Expo Risk Assess | 2011 Oct | 22007891 |
| HPLC-UV method for nicotine, strychnine, and aconitine in dairy products. | J Agric Food Chem | 2006 Oct 4 | 17002408 |
| [Scientific research related to analysis of harmful substances in foods and dietary intakes]. | Shokuhin Eiseigaku Zasshi | 2001 Aug | 11817150 |
| Effective dose in cattle of toxic alkaloids from tall larkspur (Delphinium barbeyi). | Vet Hum Toxicol | 1994 Feb | 8154094 |
| Antiarrhythmic activity of the local anaesthetic fomocaine and some of its analogues. | Arzneimittelforschung | 1989 Nov | 2619777 |
Targets
- 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
- Mechanism of Action:
- Aconitine opens voltage-gated sodium channed in the heart and other tissues.
References
- Wikipedia. Aconitine. Last Updated 11 July 2009. : http://en.wikipedia.org/wiki/Aconitine
- 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
- Mechanism of Action:
- Aconitine opens voltage-gated sodium channed in the heart and other tissues.
References
- Wikipedia. Aconitine. Last Updated 11 July 2009. : http://en.wikipedia.org/wiki/Aconitine
- 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
- Mechanism of Action:
- Aconitine opens voltage-gated sodium channed in the heart and other tissues.
References
- Wikipedia. Aconitine. Last Updated 11 July 2009. : http://en.wikipedia.org/wiki/Aconitine
- 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
- Mechanism of Action:
- Aconitine opens voltage-gated sodium channed in the heart and other tissues.
References
- Wikipedia. Aconitine. Last Updated 11 July 2009. : http://en.wikipedia.org/wiki/Aconitine
- 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
- Mechanism of Action:
- Aconitine opens voltage-gated sodium channed in the heart and other tissues.
References
- Wikipedia. Aconitine. Last Updated 11 July 2009. : http://en.wikipedia.org/wiki/Aconitine
- 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
- Mechanism of Action:
- Aconitine opens voltage-gated sodium channed in the heart and other tissues.
References
- Wikipedia. Aconitine. Last Updated 11 July 2009. : http://en.wikipedia.org/wiki/Aconitine
- 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
- Mechanism of Action:
- Aconitine opens voltage-gated sodium channed in the heart and other tissues.
References
- Wikipedia. Aconitine. Last Updated 11 July 2009. : http://en.wikipedia.org/wiki/Aconitine
- 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
- Mechanism of Action:
- Aconitine opens voltage-gated sodium channed in the heart and other tissues.
References
- Wikipedia. Aconitine. Last Updated 11 July 2009. : http://en.wikipedia.org/wiki/Aconitine
- 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
- Mechanism of Action:
- Aconitine opens voltage-gated sodium channed in the heart and other tissues.
References
- Wikipedia. Aconitine. Last Updated 11 July 2009. : http://en.wikipedia.org/wiki/Aconitine
- 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
- Mechanism of Action:
- Aconitine opens voltage-gated sodium channed in the heart and other tissues.
References
- Wikipedia. Aconitine. Last Updated 11 July 2009. : http://en.wikipedia.org/wiki/Aconitine
- 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
- Mechanism of Action:
- Aconitine opens voltage-gated sodium channed in the heart and other tissues.
References
- Wikipedia. Aconitine. Last Updated 11 July 2009. : http://en.wikipedia.org/wiki/Aconitine
- 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
- Mechanism of Action:
- Aconitine opens voltage-gated sodium channed in the heart and other tissues.
References
- Wikipedia. Aconitine. Last Updated 11 July 2009. : http://en.wikipedia.org/wiki/Aconitine
- 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
- Mechanism of Action:
- Aconitine opens voltage-gated sodium channed in the heart and other tissues.
References
- Wikipedia. Aconitine. Last Updated 11 July 2009. : http://en.wikipedia.org/wiki/Aconitine
- 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
- Mechanism of Action:
- Aconitine opens voltage-gated sodium channed in the heart and other tissues.
References
- Wikipedia. Aconitine. Last Updated 11 July 2009. : http://en.wikipedia.org/wiki/Aconitine