Brucine
(right click,save link as to download,it is a temp file,please download as soon as possible, you can also use CTRL+S to save the whole html page)
Basic Info
| Common Name | Brucine(F04790) |
| 2D Structure | |
| Description | Brucine 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. (L1227) |
| FRCD ID | F04790 |
| CAS Number | 357-57-3 |
| PubChem CID | 442021 |
| Formula | C23H26N2O4 |
| IUPAC Name | (4aR,5aS,8aR,13aS,15aS,15bR)-10,11-dimethoxy-4a,5,5a,7,8,13a,15,15a,15b,16-decahydro-2H-4,6-methanoindolo[3,2,1-ij]oxepino[2,3,4-de]pyrrolo[2,3-h]quinoline-14-one |
| InChI Key | RRKTZKIUPZVBMF-IBTVXLQLSA-N |
| InChI | InChI=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/t13-,18-,19-,21-,22-,23+/m0/s1 |
| Canonical SMILES | COC1=C(C=C2C(=C1)C34CCN5C3CC6C7C4N2C(=O)CC7OCC=C6C5)OC |
| Isomeric SMILES | COC1=C(C=C2C(=C1)[C@]34CCN5[C@H]3C[C@@H]6[C@@H]7[C@@H]4N2C(=O)C[C@@H]7OCC=C6C5)OC |
| Wikipedia | Brucine |
| Synonyms |
BRUCINE
357-57-3
Brucinum
10,11-Dimethoxystrychnine
l-Brucine
2,3-Dimethoxystrychnine
UNII-6NG17YCK6H
(-)-Brucine
Brucina
Brucin
|
| Classifies |
Plant Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Alkaloids and derivatives |
| Class | Strychnos alkaloids |
| Subclass | Not available |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Strychnos alkaloids |
| Alternative Parents |
|
| Molecular Framework | Aromatic heteropolycyclic compounds |
| 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 |
| Description | This compound 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. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 394.471 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 2 |
| Complexity | 785 |
| Monoisotopic Mass | 394.189 |
| Exact Mass | 394.189 |
| XLogP | 1 |
| Formal Charge | 0 |
| Heavy Atom Count | 29 |
| Defined Atom Stereocenter Count | 6 |
| Undefined Atom Stereocenter Count | 0 |
| 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+ | 0.9700 |
| Human Intestinal Absorption | HIA+ | 0.9837 |
| Caco-2 Permeability | Caco2+ | 0.8867 |
| P-glycoprotein Substrate | Substrate | 0.7915 |
| P-glycoprotein Inhibitor | Inhibitor | 0.8585 |
| Non-inhibitor | 0.9216 | |
| Renal Organic Cation Transporter | Inhibitor | 0.5577 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.7403 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8932 |
| CYP450 2D6 Substrate | Non-substrate | 0.7371 |
| CYP450 3A4 Substrate | Substrate | 0.8386 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.7105 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.9220 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9231 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.9223 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.8308 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.8433 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9526 |
| Non-inhibitor | 0.5582 | |
| AMES Toxicity | Non AMES toxic | 0.9132 |
| Carcinogens | Non-carcinogens | 0.9054 |
| Fish Toxicity | High FHMT | 0.9325 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.8957 |
| Honey Bee Toxicity | Low HBT | 0.6012 |
| Biodegradation | Not ready biodegradable | 1.0000 |
| Acute Oral Toxicity | III | 0.4746 |
| Carcinogenicity (Three-class) | Non-required | 0.5286 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -2.1525 | LogS |
| Caco-2 Permeability | 1.3475 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 3.3648 | LD50, mol/kg |
| Fish Toxicity | 0.2124 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.5044 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Cytotoxicity and DNA interaction of brucine and strychnine-Two alkaloids of semen strychni. | Int J Biol Macromol | 2015 | 25796448 |
| A study of Semen Strychni-induced renal injury and herb-herb interaction of Radix Glycyrrhizae extract and/or Rhizoma Ligustici extract on the comparative toxicokinetics of strychnine and brucine in rats. | Food Chem Toxicol | 2014 Jun | 24704041 |
| Dynamic detection of non-protein-bound strychnine and brucine in rabbit muscle and synovial fluid after topical application of total Strychnos alkaloid patches. | Drug Test Anal | 2014 Apr | 23776063 |
| Brucine, an alkaloid from seeds of Strychnos nux-vomica Linn., represses hepatocellular carcinoma cell migration and metastasis: the role of hypoxia inducible factor 1 pathway. | Toxicol Lett | 2013 Oct 24 | 23933019 |
| A simple method to identify the unprocessed Strychnos seeds used in herbal medicinal products. | Planta Med | 2008 Mar | 18484543 |
| The apoptotic effect of brucine from the seed of Strychnos nux-vomica on human hepatoma cells is mediated via Bcl-2 and Ca2+ involved mitochondrial pathway. | Toxicol Sci | 2006 May | 16443926 |
| Analysis of strychnine and brucine in postmortem specimens by RP-HPLC: a case report of fatal intoxication. | J Anal Toxicol | 2004 Mar | 15068571 |
Targets
- 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
- Mechanism of Action:
- Brucine acts as an antagonist at the inhibitory or strychnine-sensitive glycine receptor, a ligand-gated chloride channel in the spinal cord and the brain.
References
- 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 ]
- 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
- Mechanism of Action:
- Brucine acts as an antagonist at the inhibitory or strychnine-sensitive glycine receptor, a ligand-gated chloride channel in the spinal cord and the brain.
References
- Wikipedia. Strychnine. Last Updated 20 July 2009. : http://en.wikipedia.org/wiki/Strychnine
- 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
- Mechanism of Action:
- Brucine acts as an antagonist at the inhibitory or strychnine-sensitive glycine receptor, a ligand-gated chloride channel in the spinal cord and the brain.
References
- Wikipedia. Strychnine. Last Updated 20 July 2009. : http://en.wikipedia.org/wiki/Strychnine
- 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
- Mechanism of Action:
- Brucine acts as an antagonist at the inhibitory or strychnine-sensitive glycine receptor, a ligand-gated chloride channel in the spinal cord and the brain.
References
- Wikipedia. Strychnine. Last Updated 20 July 2009. : http://en.wikipedia.org/wiki/Strychnine
- 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
References
- 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 ]
- 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
- 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 ]
- 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
- 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 ]
- 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
- Mechanism of Action:
- Brucine acts as an antagonist at the inhibitory or strychnine-sensitive glycine receptor, a ligand-gated chloride channel in the spinal cord and the brain.
References
- Wikipedia. Strychnine. Last Updated 20 July 2009. : http://en.wikipedia.org/wiki/Strychnine
- 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
- 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 ]