Brucine (T3D3075)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (9)XML
Targets (9)
Record Information
Version2.0
Creation Date2009-07-23 18:26:04 UTC
Update Date2014-12-24 20:25:57 UTC
Accession NumberT3D3075
Identification
Common NameBrucine
ClassSmall Molecule
DescriptionBrucine is a plant toxin found in several species, most notably the Strychnine tree (Strychnos nux-vomica L.). Medically, brucine is primarily used in the regulation of high blood pressure and other comparatively benign cardiac ailments. (2)
Compound Type
  • Amide
  • Amine
  • Ether
  • Natural Compound
  • Organic Compound
  • Plant Toxin
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
(-)-brucine
10,11-Dimethoxystrychnine
10,11-Dimethystrychnine
2,3-Dimethoxy-strychnine
2,3-Dimethoxystrychnidin-10-one
2,3-Dimethoxystrychnidine-10-one
2,3-Dimethoxystrychnine
Brucin
Brucina
Brucine alkaloid
Brucinum
Dimethoxy strychnine
Indole alkaloid
Isobrucine
L-brucine
Chemical FormulaC23H26N2O4
Average Molecular Mass394.464 g/mol
Monoisotopic Mass394.189 g/mol
CAS Registry Number357-57-3
IUPAC Name4,5-dimethoxy-12-oxa-8,17-diazaheptacyclo[15.5.2.0¹,¹⁸.0²,⁷.0⁸,²².0¹¹,²¹.0¹⁵,²⁰]tetracosa-2(7),3,5,14-tetraen-9-one
Traditional Namebrucine
SMILESCOC1=CC2=C(C=C1OC)C13CCN4CC5=CCOC6CC(=O)N2C1C6C5CC34
InChI IdentifierInChI=1S/C23H26N2O4/c1-27-16-8-14-15(9-17(16)28-2)25-20(26)10-18-21-13-7-19-23(14,22(21)25)4-5-24(19)11-12(13)3-6-29-18/h3,8-9,13,18-19,21-22H,4-7,10-11H2,1-2H3
InChI KeyInChIKey=RRKTZKIUPZVBMF-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as strychnos alkaloids. These are alkaloids having a core structure based on the strychnan, stemmadenine (seco-curan), or the akuammicine (curan) skeleton.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassStrychnos alkaloids
Sub ClassNot Available
Direct ParentStrychnos alkaloids
Alternative Parents
Substituents
  • Strychnan skeleton
  • Akuammicine-skeleton
  • Stemmadenine-skeleton
  • Carbazole
  • Quinolidine
  • Indole or derivatives
  • Indolizidine
  • Anisole
  • Alkyl aryl ether
  • Delta-lactam
  • Piperidinone
  • Aralkylamine
  • Piperidine
  • Benzenoid
  • N-alkylpyrrolidine
  • Tertiary carboxylic acid amide
  • Pyrrolidine
  • Tertiary aliphatic amine
  • Tertiary amine
  • Amino acid or derivatives
  • Lactam
  • Carboxamide group
  • Azacycle
  • Oxacycle
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Ether
  • Dialkyl ether
  • Hydrocarbon derivative
  • Amine
  • Organopnictogen compound
  • Organic oxide
  • Carbonyl group
  • Organic oxygen compound
  • Organonitrogen compound
  • Organooxygen compound
  • Organic nitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point178°C
Boiling PointNot Available
Solubility3.2 mg/mL at 15°C [YALKOWSKY,SH & DANNENFELSER,RM (1992)]
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.32 g/LALOGPS
logP1.85ALOGPS
logP0.61ChemAxon
logS-3.1ALOGPS
pKa (Strongest Acidic)17.24ChemAxon
pKa (Strongest Basic)8.85ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area51.24 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity107.43 m³·mol⁻¹ChemAxon
Polarizability41.98 ųChemAxon
Number of Rings7ChemAxon
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, Positivesplash10-0udi-0009000000-9ab15bf460468b70f9282021-09-24View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-01yo-0195000000-eae039134db6933f60762021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-0002-0009000000-73d742bb3c4eabe4901e2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-0002-0009000000-41fe1ffbf7c12ef45f6e2021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-0009000000-b5d95786b28beaef339d2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0002-0009000000-8bc90ab344491204f55e2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-05nf-0039000000-f2335461f64375e40c9e2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-0009000000-7acb0d26429fdd2091532016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0006-0009000000-0f551d37cae34ddb3bb72016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-000g-3029000000-788a525198ca58efb2e92016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-0009000000-8d2cc2bffa4a115e54982021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0002-0009000000-8d2cc2bffa4a115e54982021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-002b-0009000000-dc32b4b2d0c882d4ad912021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-0009000000-c89f5798c7f5c75bb99e2021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0006-0009000000-90711b505cdaed4588ae2021-10-12View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0007-0009000000-b81cf979742604114b8c2021-10-12View Spectrum
Toxicity Profile
Route of ExposureOral (ingestion) (5) ; dermal (5)
Mechanism of ToxicityBrucine acts as an antagonist at the inhibitory or strychnine-sensitive glycine receptor, a ligand-gated chloride channel in the spinal cord and the brain. (4)
MetabolismNot Available
Toxicity ValuesLD50: 4 mg/kg (Oral, Rat) (1) LD50: 91 mg/kg (Intraperitoneal, Rat) (1) LD50: 60 mg/kg (Subcutaneous, Rat) (1)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesBrucine is a plant toxin found in several species, most notably the Strychnine tree (Strychnos nux-vomica L.). Medically, brucine is primarily used in the regulation of high blood pressure and other comparatively benign cardiac ailments. (2)
Minimum Risk LevelNot Available
Health EffectsDeath may result from asphyxia or sheer exhaustion. (2)
SymptomsBrucine causes muscular convulsions of increasing intensity and frequency and eventually death through asphyxia or sheer exhaustion. (2)
TreatmentTreatment of brucine poisoning involves an oral application of an activated charcoal infusion to absorb any poison within the digestive tract that has not yet been absorbed into the blood. Anticonvulsants such as phenobarbital or diazepam are administered to control convulsions, along with muscle relaxants such as dantrolene to combat muscle rigidity. (3)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID442021
ChEMBL IDNot Available
ChemSpider IDNot Available
KEGG IDC09084
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDBrucine
PDB IDNot Available
ACToR ID7136
Wikipedia LinkBrucine
References
Synthesis ReferenceNot Available
MSDST3D3075.pdf
General References
  1. Lewis RJ (1996). Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold.
  2. Wikipedia. Brucine. Last Updated 8 April 2009. [Link]
  3. Wikipedia. Strychnine poisoning. Last Updated 25 June 2009. [Link]
  4. Wikipedia. Strychnine. Last Updated 20 July 2009. [Link]
  5. Wikipedia. Phytotoxin. Last Updated 7 August 2009. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

Target Details
1. Glycine receptor subunit alpha-1
General Function:
Transmitter-gated ion channel activity
Specific Function:
The glycine receptor is a neurotransmitter-gated ion channel. Binding of glycine to its receptor increases the chloride conductance and thus produces hyperpolarization (inhibition of neuronal firing).
Gene Name:
GLRA1
Uniprot ID:
P23415
Molecular Weight:
52623.35 Da
References
  1. Jensen AA, Gharagozloo P, Birdsall NJ, Zlotos DP: Pharmacological characterisation of strychnine and brucine analogues at glycine and alpha7 nicotinic acetylcholine receptors. Eur J Pharmacol. 2006 Jun 6;539(1-2):27-33. Epub 2006 May 9. [16687139 ]
  2. Wikipedia. Strychnine. Last Updated 20 July 2009. [Link]
Target Details
2. Glycine receptor subunit alpha-2
General Function:
Transmitter-gated ion channel activity
Specific Function:
The glycine receptor is a neurotransmitter-gated ion channel. Binding of glycine to its receptor increases the chloride conductance and thus produces hyperpolarization (inhibition of neuronal firing).
Gene Name:
GLRA2
Uniprot ID:
P23416
Molecular Weight:
52001.585 Da
References
  1. Wikipedia. Strychnine. Last Updated 20 July 2009. [Link]
Target Details
3. Glycine receptor subunit alpha-3
General Function:
Transmitter-gated ion channel activity
Specific Function:
The glycine receptor is a neurotransmitter-gated ion channel. Binding of glycine to its receptor increases the chloride conductance and thus produces hyperpolarization (inhibition of neuronal firing).
Gene Name:
GLRA3
Uniprot ID:
O75311
Molecular Weight:
53799.775 Da
References
  1. Wikipedia. Strychnine. Last Updated 20 July 2009. [Link]
Target Details
4. Glycine receptor subunit alpha-4
General Function:
Transmitter-gated ion channel activity
Specific Function:
The glycine receptor is a neurotransmitter-gated ion channel. Binding of glycine to its receptor increases the chloride conductance and thus produces hyperpolarization (inhibition of neuronal firing).
Gene Name:
GLRA4
Uniprot ID:
Q5JXX5
Molecular Weight:
47727.92 Da
References
  1. Wikipedia. Strychnine. Last Updated 20 July 2009. [Link]
Target Details
5. Glycine receptor subunit beta
General Function:
Glycine binding
Specific Function:
The glycine receptor is a neurotransmitter-gated ion channel. Binding of glycine to its receptor increases the chloride conductance and thus produces hyperpolarization (inhibition of neuronal firing).
Gene Name:
GLRB
Uniprot ID:
P48167
Molecular Weight:
56121.62 Da
References
  1. Wikipedia. Strychnine. Last Updated 20 July 2009. [Link]
Target Details
6. Muscarinic acetylcholine receptor M1
General Function:
Phosphatidylinositol phospholipase c activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM1
Uniprot ID:
P11229
Molecular Weight:
51420.375 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory44.66836 uMNot AvailableBindingDB 50401037
References
  1. Daval SB, Valant C, Bonnet D, Kellenberger E, Hibert M, Galzi JL, Ilien B: Fluorescent derivatives of AC-42 to probe bitopic orthosteric/allosteric binding mechanisms on muscarinic M1 receptors. J Med Chem. 2012 Mar 8;55(5):2125-43. doi: 10.1021/jm201348t. Epub 2012 Feb 27. [22329602 ]
Target Details
7. Muscarinic acetylcholine receptor M2
General Function:
G-protein coupled acetylcholine receptor activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol.
Gene Name:
CHRM2
Uniprot ID:
P08172
Molecular Weight:
51714.605 Da
References
  1. Jakubik J, Krejci A, Dolezal V: Asparagine, valine, and threonine in the third extracellular loop of muscarinic receptor have essential roles in the positive cooperativity of strychnine-like allosteric modulators. J Pharmacol Exp Ther. 2005 May;313(2):688-96. Epub 2005 Jan 12. [15647330 ]
Target Details
8. Muscarinic acetylcholine receptor M3
General Function:
Receptor activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM3
Uniprot ID:
P20309
Molecular Weight:
66127.445 Da
References
  1. Stewart GD, Sexton PM, Christopoulos A: Prediction of functionally selective allosteric interactions at an M3 muscarinic acetylcholine receptor mutant using Saccharomyces cerevisiae. Mol Pharmacol. 2010 Aug;78(2):205-14. doi: 10.1124/mol.110.064253. Epub 2010 May 13. [20466821 ]
Target Details
9. Muscarinic acetylcholine receptor M4
General Function:
Guanyl-nucleotide exchange factor activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase.
Gene Name:
CHRM4
Uniprot ID:
P08173
Molecular Weight:
53048.65 Da
References
  1. Lanzafame AA, Sexton PM, Christopoulos A: Interaction studies of multiple binding sites on m4 muscarinic acetylcholine receptors. Mol Pharmacol. 2006 Aug;70(2):736-46. Epub 2006 May 18. [16709648 ]