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Record Information
Version2.0
Creation Date2014-08-29 05:05:20 UTC
Update Date2014-12-24 20:26:38 UTC
Accession NumberT3D4087
Identification
Common NameChelidonine
ClassSmall Molecule
DescriptionChelidonine is an isolate of Papaveraceae with acetylcholinesterase and butyrylcholinesterase inhibitory activity.
Compound Type
  • Amine
  • Natural Compound
  • Organic Compound
  • Plant Toxin
Chemical Structure
Thumb
Synonyms
Synonym
(+)-Chelidonine
Chelidonin
Helidonine
Khelidonin
Stylophorin
Chemical FormulaC20H19NO5
Average Molecular Mass353.369 g/mol
Monoisotopic Mass353.126 g/mol
CAS Registry Number476-32-4
IUPAC Name(1S,12S,13R)-24-methyl-5,7,18,20-tetraoxa-24-azahexacyclo[11.11.0.0²,¹⁰.0⁴,⁸.0¹⁴,²².0¹⁷,²¹]tetracosa-2,4(8),9,14(22),15,17(21)-hexaen-12-ol
Traditional Namechelidonine
SMILES[H][C@]1(O)CC2=CC3=C(OCO3)C=C2[C@@]2([H])N(C)CC3=C(C=CC4=C3OCO4)[C@@]12[H]
InChI IdentifierInChI=1S/C20H19NO5/c1-21-7-13-11(2-3-15-20(13)26-9-23-15)18-14(22)4-10-5-16-17(25-8-24-16)6-12(10)19(18)21/h2-3,5-6,14,18-19,22H,4,7-9H2,1H3/t14-,18-,19+/m0/s1
InChI KeyInChIKey=GHKISGDRQRSCII-ZOCIIQOWSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as hexahydrobenzophenanthridine alkaloids. These are alkaloids containing a hexahydrobenzophenanthridine skeleton, which is a tetracyclic compound containing a benzene fused to a hexahydrophenanthridine moiety.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassBenzophenanthridine alkaloids
Sub ClassHexahydrobenzophenanthridine alkaloids
Direct ParentHexahydrobenzophenanthridine alkaloids
Alternative Parents
Substituents
  • Hexahydrobenzophenanthridine alkaloid skeleton
  • Benzoquinoline
  • Phenanthridine
  • Quinoline
  • Tetrahydroisoquinoline
  • Tetralin
  • Benzodioxole
  • Aralkylamine
  • Benzenoid
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary alcohol
  • Acetal
  • Azacycle
  • Oxacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organopnictogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytosol
  • Extracellular
  • Membrane
  • Mitochondrion
  • Tubulin
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
ApoptosisNot Availablemap04210
Cell cycleNot Availablemap04110
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 Solubility0.86 g/LALOGPS
logP1.77ALOGPS
logP2.05ChemAxon
logS-2.6ALOGPS
pKa (Strongest Acidic)14.64ChemAxon
pKa (Strongest Basic)5.73ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area60.39 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity93.01 m³·mol⁻¹ChemAxon
Polarizability37.32 ųChemAxon
Number of Rings6ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udr-0009000000-22778898ff72b0162b30JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0fe0-0129000000-74a8ffacab86305eef82JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4l-0196000000-1ae250beb7f61d7d4016JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-0009000000-d9a884c37dc41dd2ccbbJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0ue9-0009000000-c1358c2c0bbf8c7cba2dJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0089-2098000000-85918c28d8e3ec7e5e57JSpectraViewer
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityChelidonine 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. Chelidonine has an acetylcholinesterase and butyrylcholinesterase inhibitory activity. (Wikipedia) Generally, some of the alkaloid extract from Chelidonium majus, which contains protoberberine and benzo[c]phenanthridine alkaloids such as chelidonine, intercalate DNA, and in consequence inhibit DNA and RNA polymerase, topoisomerase, telomerase, and even ribosomal protein biosynthesis or bind to tubulin/microtubules, thus acting as spindle poisons. Chelidonine has the ability to overcome multidrug resistance (MDR) of different cancer cell lines through interaction with ABC-transporters, CYP3A4 and GST, by induction of apoptosis, and cytotoxic effects. It induced apoptosis in MDR cells which was accompanied by an activation of caspase-3, -8,-6/9, and phosphatidyl serine (PS) exposure. (1) Chelidonine is known to cause mitotic arrest and to interact weakly with tubulin. Chelidonine has proven to be a weak inhibitor of cell growth in two normal (monkey kidney and Hs27), two transformed (Vero and Graham 293) and two malignant (WHCO5 and HeLa) cell lines. (2)
MetabolismParaoxonase (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 OP 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 ID197810
ChEMBL IDCHEMBL496867
ChemSpider ID171216
KEGG IDC12242
UniProt IDNot Available
OMIM ID
ChEBI IDCHEBI:31389
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDST3D4087.pdf
General References
  1. El-Readi MZ, Eid S, Ashour ML, Tahrani A, Wink M: Modulation of multidrug resistance in cancer cells by chelidonine and Chelidonium majus alkaloids. Phytomedicine. 2013 Feb 15;20(3-4):282-94. doi: 10.1016/j.phymed.2012.11.005. Epub 2012 Dec 11. [23238299 ]
  2. Panzer A, Joubert AM, Bianchi PC, Hamel E, Seegers JC: The effects of chelidonine on tubulin polymerisation, cell cycle progression and selected signal transmission pathways. Eur J Cell Biol. 2001 Jan;80(1):111-8. [11211931 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available