CHELIDONINE CAS 476-32-4
CHELIDONINE Basic informationDescription Uses Pharmacological action
| Product Name: | CHELIDONINE |
| Synonyms: | chelidoniny;helidonine;khelidonin;STYLOPHORIN;STYLOPHORINE;STYLOPHORON;Chelidonine 476-32-4;CHELIDONIN |
| CAS: | 476-32-4 |
| MF: | C20H19NO5 |
| MW: | 353.37 |
| EINECS: | 207-504-1 |
| Product Categories: | Alkaloids |
| Mol File: | 476-32-4.mol |
CHELIDONINE Chemical Properties
| Melting point | 135-140°C |
| alpha | D22 +115 ±3° (ethanol); D20 +117° (c = 3 in CHCl3) |
| Boiling point | bp0.002 220° (air-bath temp) |
| density | 1.2976 (rough estimate) |
| refractive index | 1.5800 (estimate) |
| storage temp. | Sealed in dry,2-8°C |
| solubility | Soluble in chloroform; slightly soluble in methan |
| pka | 14.11±0.20(Predicted) |
| form | powder |
| color | Colorless |
| Merck | 13,2061 |
| Cosmetics Ingredients Functions | SKIN CONDITIONING |
| InChI | InChI=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 |
| InChIKey | GHKISGDRQRSCII-ZOCIIQOWSA-N |
| SMILES | [C@@H]1(O)[C@@]2([H])[C@]([H])(N(C)CC3=C2C=CC2OCOC3=2)C2C=C3OCOC3=CC=2C1 |
| LogP | 2.899 (est) |
| CAS DataBase Reference | 476-32-4(CAS DataBase Reference) |
Safety Information
| Hazard Codes | Xn |
| Risk Statements | 25-20/21/22 |
| Safety Statements | 20-45-36/37 |
| RIDADR | 2811 |
| WGK Germany | 3 |
| RTECS | FL9450000 |
| Storage Class | 6.1C - Combustible acute toxic Cat.3 toxic compounds or compounds which causing chronic effects |
| Hazard Classifications | Acute Tox. 3 Inhalation Acute Tox. 3 Oral |
| Toxicity | LD50 in mice (mg/kg): 34.6 ±2.44 i.v. (Anderson, Chen) |
| Description | Chelidonine, also named ranunculine, is a benzophenanthridine alkaloid isolated from the whole plant of Chelidonium majus. L. It has been used as a painkiller in clinical treatment based on its morphine-like analgesic effect. Pharmacological researches in recent years have demonstrated that chelidonine played a role in antitumor, antibacterial, spasmolysis activities, and so on. And the antitumor activity is drawing more and more attention. However, its mechanisms of function remain unclear, which needs to be clarified in the future. |
| Uses | Chelidonine is the major alkaloid component of Chelidonium majus. Chelidonium majus L. is the only species of the tribe Chelidonieae of the Papaveraceae family. The Papaveraceae family is rich in specific alkaloids. C. majus contains various isoquinoline alkaloids with protopine, protoberberine and benzophenanthridine structures. This benzophenanthridine alkaloid can induce apoptosis in some transformed or malignant cell lines. D-Chelidonine, the main alkaloid of Chelidonium majus, was first isolated in 1839. |
| Pharmacological action | Chelidonine is an isolate of Papaveraceae with acetylcholinesterase and butyrylcholinesterase (a nonspecific cholinesterase) inhibitory activity. AChE (acetylcholinesterase) inhibitors or anti-cholinesterases inhibit the cholinesterase enzyme from breaking down ACh, increasing both the level and duration of the neurotransmitter action. According to the mode of action, AChE inhibitors can be divided into two groups: irreversible and reversible. Reversible inhibitors, competitive or noncompetitive, mostly have therapeutic applications, while toxic effects are associated with irreversible AChE activity modulators. Reversible AChE inhibitors play an important role in pharmacological manipulation of the enzyme activity. These inhibitors include compounds with different functional groups (carbamate, quaternary or tertiary ammonium group), and have been applied in the diagnostic and/or treatment of various diseases such as: myasthenia gravis, AD, post-operative ileus, bladder distention, glaucoma, as well as antidote to anticholinergic overdose. In general, methyltransferases of BIA metabolism accept a wide variety of alkaloid substrates with diverse backbone structures, with some showing more flexibility than others with respect to substrate range. |
| Description | Chelidonine is a benzophenanthridine alkaloid that has been isolated from C. majus. It induces Bcl-2- and caspase-dependent apoptosis in HepG2 human liver carcinoma cells with an LC50 value of 12 μM and in Jurkat human T cells when used at a concentration of 1 μM. Chelidonine also downregulates hTERT expression in HepG2 cells, reduces telomerase activity, and induces cell senescence. |
| Description | Chelidonine, also named ranunculine, is a kind of alkaloid isolated from the wholeplant of Chelidonium majus. L . As a kind of traditional Chinese medicine,Chelidonium majus. L was firstly recorded in Chiu Huang Pen Ts’ao of Mingdynasty. In the seventeenth century, it has been used for the treatment of jaundice,biliary colic, and cholelithiasis. In 1941, a researcher from Soviet Union reportedthat it showed good effect for the treatment of cutaneous tuberculosis. This plant hasmultiple effects on different diseases, including anti-inflammatory, analgesia,relieving cough, inducing diuresis, anticancer, antifungal, relieving asthma, anddetoxification. It was recorded in the Pharmacopoeia of the People’s Republic ofChina (1977) . The material basis for Chelidonium majus. L is alkaloid. Among which, chelidonine,a benzophenanthridine alkaloid, is the main effective ingredient . Althoughgreat progresses have been made in the chemical synthesis of chelidonine recently,the biosynthetic pathways of chelidonine remain unclear, which still need in-depthstudy and exploration in the future |
| Chemical Properties | White, crystalline powder alkaloid. |
| Physical properties | Appearance: white crystal or crystalline powder, monoclinic prism crystal.Solubility: insoluble in water; soluble in ethanol, chloroform, and amyl alcohol.Melting point: 135–136 °C. Boiling point: 220 °C. Specific optical rotation: +115°. |
| History | Chelidonine was isolated from Chelidonium majus. L in 1824 for the first time.Pharmacological studies found that it exerted antitumor effect via different mechanisms.However, its poor bioavailability limited its application. Some researchers developed a chelidonine/polylactic acid copolymer nanoparticle using nanotechnology.The nano-chelidonine showed good tissue distribution without causing anytoxicity in mice and could enter into the brain tissues, showing great applicationpotential. In addition, nano-chelidonine showed protective effect on liver injuryinduced by cadmium in mice . In 1981, an Austrian researcher isolated a novel compound ukrain (phosphorothioatederivative of chelidonine) from Chelidonium majus. L. Ukrain could inhibittumor cell proliferation through a variety of mechanisms. Currently, ukrain is usedas an antitumor drug for the clinical treatment of lung cancer, breast cancer, prostatecancer, and pancreatic cancer . In 2004, quarter amine chelidonine phosphorothioatederivatives have been applied for an invention patent as anticancer drugs inChina. Chelidonine has morphine-like analgesic effects suggesting that its analgesiceffect is mainly peripheral and cannot be antagonized by the morphine receptorantagonist naloxone . The 6-alkoxy and 6-acyloxy derivatives of chelidonine caninhibit the central nervous system, especially for nerve terminal, and show sedativeand hypnotic effects . |
| Uses | Poison; central nervous system depres-sant causing sleepiness, depression, slowing of thepulse, coma and circulatory failure. |
| Definition | ChEBI: Chelidonine is an alkaloid fundamental parent, a benzophenanthridine alkaloid and an alkaloid antibiotic. |
| Biochem/physiol Actions | Inhibits tubulin polymerisation (IC50=24 μM), thereby disrupting microtubule structure in cells and inducing a G2/M mitotic arrest. |
| Pharmacology | Chelidonine has a variety of pharmacological effects, mainly manifested in the followingaspects: 1. The effect on nervous system (analgesia, sedation) Chelidonine, as a protopine, has analgesia effect similar to that of morphine.After intragastric administration (5–20 mg/kg) to mice, it showed a dose-dependentanalgesic effect, which could sustain 4–48 h . Chelidonine derivatives also havesedative and hypnotic effects . 2. The effect on cardiovascular systemChelidonine has many effects on cardiovascular system, including exciting heart,expanding coronary blood vessels, and increasing blood pressure. Chelidonine(0.01–0.02 mg) leads to the excitement of frog heart in vitro, as well as slowdownof heart beat. Higher dosage (0.05 mg) of chelidonine could cause arrhythmia anddiastolic cardiac arrest . 3. The antitumor effect Chelidonine is a toxic substance that can influence mitosis. In vitro studies haveshown that chelidonine had significant inhibitory effects for gastric cancer, leukemia,nasopharyngeal carcinoma, and hepatoma carcinoma cells. It also could delaythe growth of malignant tumors. Its antitumor effects were mediated by differentmechanisms, which still need further studies . 4. The effect on smooth muscle Chelidonine has spasmolytic and diastolic effects and can inhibit a variety ofsmooth muscle spasm. Obvious spasmolytic effects for gastrointestinal tract andbronchial and urinary system have been reported . 5. The antibacterial effect Chelidonine has antibacterial effect. It inhibits Mycobacterium tuberculosisin vivo and inhibits alpha Streptococcus, Diplococcus pneumoniae, and other gram-positivebacteria in vitro. In addition, chelidonine also shows inhibitory effect onKauffman-Wolf Trichophyta and Epidermophyton floccosum . 6. Other pharmacological effects Chelidonine showed protective effects on cadmium chloride-induced liver andkidney toxicity in rats. Chelidonine can inhibit the growth of human keratinocytes.Guinea pig test confirmed that chelidonine (4–10 mg/kg) could prevent or delay theanaphylactic shock. In addition, chelidonine has anti-mite effect and good synergisticeffect with trichlorfon or omethoate to prevent cotton bollworm. |
| Clinical Use | Chelidonine has been used as a painkiller in clinical application due to its significantanalgesic effect. Chelidonine phosphate can be used for treatment of gastrointestinaland ulcer pain, as a substitute of morphine preparations. Wei Tong Shu capsuleis used to treat pain caused by gastric convulsion, chronic gastritis, gastric ulcer, andduodenal ulcer. Its main effective compositions are chelidonine and protopine. FuFang Zhong Yao Tong An injection has collateral dredging and analgesic effects andcan be used for the treatment of moderate pain caused by chemoradiotherapy ornon-chemoradiotherapy of gastric cancer, lung cancer, and liver cancer. Its twomain components are chelidonine and sinomenine. Ukrain (NSC-631570), a phosphorothioatederivative of chelidonine, has been used in clinical treatment as aneffective antitumor drug for the treatment of lung cancer, breast cancer, prostatecancer, and pancreatic cancer. |
| References | [1] SAKINEH KAZEMI NOUREINI Michael W. Transcriptional down regulation of hTERT and senescence induction in HepG2 cells by chelidonine.[J]. World Journal of Gastroenterology, 2009: 3603-3610. DOI: 10.3748/wjg.15.3603 [2] ANNA OCH. UPLC-MS/MS Profile of Alkaloids with Cytotoxic Properties of Selected Medicinal Plants of the Berberidaceae and Papaveraceae Families.[J]. Oxidative Medicine and Cellular Longevity, 2017: 9369872. DOI: 10.1155/2017/9369872 [3] DANIEL HABERMEHL. Proapoptotic activity of Ukrain is based on Chelidonium majus L. alkaloids and mediated via a mitochondrial death pathway.[J]. BMC Cancer, 2006, 6: 14. DOI: 10.1186/1471-2407-6-14 |
CHELIDONINE Preparation Products And Raw materials
| Raw materials | 1,3-Benzodioxole-4-carboxaldehyde, 5-iodo- |
