T3DB: Protopine

Identification Taxonomy Biological Properties Physical Properties Toxicity Profile Spectra Concentrations Links References Gene Regulation XML

Record Information

Version

2.0

Creation Date

2014-08-29 04:49:13 UTC

Update Date

2014-12-24 20:26:35 UTC

Accession Number

T3D4015

Identification

Common Name

Protopine

Class

Small Molecule

Description

Protopine is a benzylisoquinoline alkaloid occurring in opium poppies and other plants of the family papaveraceae. It has been found to inhibit histamine H1 receptors and platelet aggregation, and acts as an opioid analgesic.

Compound Type

Amine
Ester
Food Toxin
Metabolite
Natural Compound
Organic Compound
Plant Toxin

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Synonym
Biflorine
Corydinine
Fumarine
Hypercorine
Macleyine
Protopin

Chemical Formula

C₂₀H₁₉NO₅

Average Molecular Mass

353.369 g/mol

Monoisotopic Mass

353.126 g/mol

CAS Registry Number

130-86-9

IUPAC Name

15-methyl-7,9,19,21-tetraoxa-15-azapentacyclo[15.7.0.0⁴,¹².0⁶,¹⁰.0¹⁸,²²]tetracosa-1(17),4(12),5,10,18(22),23-hexaen-3-one

Traditional Name

protopine

SMILES

CN1CCC2=CC3=C(OCO3)C=C2C(=O)CC2=C(C1)C1=C(OCO1)C=C2

InChI Identifier

InChI=1S/C20H19NO5/c1-21-5-4-13-7-18-19(25-10-24-18)8-14(13)16(22)6-12-2-3-17-20(15(12)9-21)26-11-23-17/h2-3,7-8H,4-6,9-11H2,1H3

InChI Key

InChIKey=GPTFURBXHJWNHR-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as protopine alkaloids. These are alkaloids with a structure based on a tricyclic protopine formed by oxidative ring fission of protoberberine N-metho salts.

Kingdom

Organic compounds

Super Class

Alkaloids and derivatives

Class

Protopine alkaloids

Sub Class

Not Available

Direct Parent

Protopine alkaloids

Alternative Parents

Substituents

Protopine skeleton
Benzodioxole
Aryl ketone
Aryl alkyl ketone
Aralkylamine
Benzenoid
Ketone
Tertiary amine
Tertiary aliphatic amine
Acetal
Oxacycle
Azacycle
Organoheterocyclic compound
Organic oxide
Organopnictogen compound
Organooxygen compound
Organonitrogen compound
Organic oxygen compound
Hydrocarbon derivative
Amine
Organic nitrogen compound
Aromatic heteropolycyclic compound

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

dibenzazecine alkaloid (CHEBI:16415 )
Isoquinoline alkaloids (C05189 )
a small molecule (PROTOPINE )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

Cellular Locations

Membrane

Biofluid Locations

Not Available

Tissue Locations

Kidney

Pathways

Not Available

Applications

Not Available

Biological Roles

metabolite

Chemical Roles

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	208°C
Boiling Point	Not Available
Solubility	Not Available
LogP	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.2 g/L	ALOGPS
logP	1.95	ALOGPS
logP	2.59	ChemAxon
logS	-3.2	ALOGPS
pKa (Strongest Acidic)	15.82	ChemAxon
pKa (Strongest Basic)	4.95	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	6	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	57.23 Å²	ChemAxon
Rotatable Bond Count	0	ChemAxon
Refractivity	94.57 m³·mol⁻¹	ChemAxon
Polarizability	36.68 Å³	ChemAxon
Number of Rings	5	ChemAxon
Bioavailability	1	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
GC-MS	GC-MS Spectrum - GC-MS (1 TMS)	splash10-004r-2931000000-d14db9f8fbba357a7cea	2014-06-16	View Spectrum
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-004r-2931000000-d14db9f8fbba357a7cea	2017-09-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-00ri-2049000000-c70fb92c70c89eb31559	2017-09-01	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-0f79-0936000000-da2afff6dba215da666a	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-000i-0931000000-3ae8ba25a400b3cfc336	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-0udi-0009000000-d474e4da85bfe6b8622e	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-0udi-0009000000-c77daec49f175e0080d3	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-0udi-0629000000-f410a01812829c61b1b5	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-000i-0921000000-cb2a7100722bf81f462f	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QQ , positive	splash10-000i-0930000000-e740d177ef096526ca53	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-IT , positive	splash10-000j-0932000000-899dc6a90055430abee2	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-0udi-0009000000-1833ae0a6ab82f156d51	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-0udr-0938000000-8a5ae3db2af3946a0e75	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - LC-ESI-QTOF , positive	splash10-000i-0920000000-925c965ff2b76b30d02f	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - , positive	splash10-0f79-0944000000-e1624142a49564f32b99	2017-09-14	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 6V, Positive	splash10-000i-0910000000-79485782e2b17a1fccef	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 6V, Positive	splash10-000i-0931000000-a9d401bee935049397de	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 6V, Positive	splash10-000i-0920000000-092e042fc79ca310c193	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 6V, Positive	splash10-000i-0941000000-1fdf197d94d08c882c08	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 10V, Positive	splash10-0udi-0009000000-aab71a61504570b7beeb	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 20V, Positive	splash10-0udr-0928000000-60509c382ac86776f91c	2021-09-20	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum - 40V, Positive	splash10-000i-0920000000-925c965ff2b76b30d02f	2021-09-20	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-0udi-0009000000-0089e0012db766e23529	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-0udj-0509000000-ed54f57036aee6ac913c	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-004j-1900000000-e130dfa9e240571ed4e0	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0udi-0009000000-400e98b52794a7bf4fbd	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0udi-0009000000-71833c50697c0a4e532c	2016-08-03	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-002f-9658000000-c8824149cc8b247dcb6f	2016-08-03	View Spectrum
MS	Mass Spectrum (Electron Ionization)	splash10-0002-2910000000-c237219498d206631a06	2014-09-20	View Spectrum

Toxicity Profile

Route of Exposure

Not Available

Mechanism of Toxicity

Protopine has been found to inhibit histamine H1 receptors and platelet aggregation, and acts as an analgesic. It is one of the compounds with activity like OPIATE ALKALOIDS, acting at OPIOID RECEPTORS. Properties include induction of ANALGESIA or NARCOSIS. Protopine can selectively bind to but do not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine. Classical antihistaminics antagonize or prevent the action of histamine mainly in immediate hypersensitivity. They act in the bronchi, capillaries, and some other smooth muscles, and are used to prevent or allay motion sickness, seasonal rhinitis, and allergic dermatitis and to induce somnolence. Protopine can also function as platelet aggregation inhibitors which antagonize or impair any mechanism leading to blood platelet aggregation, whether during the phases of activation and shape change or following the dense-granule release reaction and stimulation of the prostaglandin-thromboxane system. Protopine inhibits the contractility of isolated cardiac papillary muscles and the proliferation of vascular smooth muscle cells induced by endothelin. It also shortens action potential duration and prolongs the effective refractory period in guinea pig cardiac papillary muscles. The protective effect on rat heart from ischemia_reperfusion damage and the relaxation of rat thoracic aorta induced by protopine have been related to the inhibition of Ca2+ influx through both voltage- and receptor-operated Ca2+ channels. Protopine has been the focus of a large number of biological studies in which they both exhibited, for instance, anti-parasitic activity and only weak cytotoxicity in comparison with other types of isoquinoline alkaloids. Protopine was found to be cytoprotective against oxidative stress induced cell death in vitro. The alkaloid was shown to have anti-arrhythmic, anti-thrombotic, anti-inflammatory, and hepatoprotective effects in animal models. The biological activity of protopine may be associated with its ability to inhibit calcium, sodium, and potassium channels. (PMID:15588728; PMID:21419197; L2104)

Metabolism

Not Available

Toxicity Values

Not Available

Lethal Dose

Not Available

Carcinogenicity (IARC Classification)

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

Uses/Sources

It has been found to inhibit histamine H1 receptors and platelet aggregation, and acts as an opioid analgesic.

Minimum Risk Level

Not Available

Health Effects

Not Available

Symptoms

Not Available

Treatment

Not Available

Normal Concentrations

Not Available

Abnormal Concentrations

Not Available

External Links

DrugBank ID

Not Available

HMDB ID

PubChem Compound ID

ChEMBL ID

ChemSpider ID

KEGG ID

UniProt ID

Not Available

OMIM ID

ChEBI ID

16415

BioCyc ID

6-HYDROXYPROTOPINE

CTD ID

Not Available

Stitch ID

Not Available

PDB ID

Not Available

ACToR ID

Not Available

Wikipedia Link

Not Available

References

Synthesis Reference

Rueffer, M.; Zenk, M. H. Enzymatic formation of protopines by a microsomal cytochrome P-450 system of Corydalis vaginans. Tetrahedron Letters (1987), 28(44), 5307-10.

MSDS

Link

General References

Paul LD, Maurer HH: Studies on the metabolism and toxicological detection of the Eschscholtzia californica alkaloids californine and protopine in urine using gas chromatography-mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Jun 5;789(1):43-57. [12726842 ]
Wynne PM, Vine JH, Amiet RG: Protopine alkaloids in horse urine. J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Nov 5;811(1):85-91. [15458726 ]
Jiang B, Cao K, Wang R: Inhibitory effect of protopine on K(ATP) channel subunits expressed in HEK-293 cells. Eur J Pharmacol. 2004 Dec 15;506(2):93-100. [15588728 ]
pubchem [Link]

Gene Regulation

Up-Regulated Genes

Not Available

Down-Regulated Genes

Not Available

Protopine (T3D4015)

Structure for T3D4015: Protopine