476-32-4 Usage
Uses
Used in Pharmaceutical Industry:
Chelidonine is used as a painkiller for its morphine-like analgesic effect.
Used in Traditional Chinese Medicine:
Chelidonine is used for the treatment of jaundice, biliary colic, cholelithiasis, cutaneous tuberculosis, and other diseases, including anti-inflammatory, analgesia, relieving cough, inducing diuresis, anticancer, antifungal, relieving asthma, and detoxification.
Used in Antitumor Applications:
Chelidonine is used as an antitumor agent, inducing Bcl-2and caspase-dependent apoptosis in HepG2 human liver carcinoma cells and Jurkat human T cells.
Used in Alkaloid Research:
Chelidonine is used as a major effective ingredient in the study of benzophenanthridine alkaloids and their biosynthetic pathways.
Used in Poison:
Chelidonine can be used as a poison, acting as a central nervous system depressant causing sleepiness, depression, slowing of the pulse, coma, and circulatory failure. However, this use is not recommended due to its harmful effects.
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.
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 any
toxicity in mice and could enter into the brain tissues, showing great application
potential. In addition, nano-chelidonine showed protective effect on liver injury
induced by cadmium in mice .In 1981, an Austrian researcher isolated a novel compound ukrain (phosphorothioate
derivative of chelidonine) from Chelidonium majus. L. Ukrain could inhibit
tumor cell proliferation through a variety of mechanisms. Currently, ukrain is used
as an antitumor drug for the clinical treatment of lung cancer, breast cancer, prostate
cancer, and pancreatic cancer . In 2004, quarter amine chelidonine phosphorothioate
derivatives have been applied for an invention patent as anticancer drugs in
China.Chelidonine has morphine-like analgesic effects suggesting that its analgesic
effect is mainly peripheral and cannot be antagonized by the morphine receptor
antagonist naloxone . The 6-alkoxy and 6-acyloxy derivatives of chelidonine can
inhibit the central nervous system, especially for nerve terminal, and show sedative
and hypnotic effects .
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 following
aspects: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-dependent
analgesic effect, which could sustain 4–48 h . Chelidonine derivatives also have
sedative 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 slowdown
of heart beat. Higher dosage (0.05 mg) of chelidonine could cause arrhythmia and
diastolic cardiac arrest .3. The antitumor effectChelidonine is a toxic substance that can influence mitosis. In vitro studies have
shown that chelidonine had significant inhibitory effects for gastric cancer, leukemia,
nasopharyngeal carcinoma, and hepatoma carcinoma cells. It also could delay
the growth of malignant tumors. Its antitumor effects were mediated by different
mechanisms, which still need further studies .4. The effect on smooth muscleChelidonine has spasmolytic and diastolic effects and can inhibit a variety of
smooth muscle spasm. Obvious spasmolytic effects for gastrointestinal tract and
bronchial and urinary system have been reported .5. The antibacterial effectChelidonine has antibacterial effect. It inhibits Mycobacterium tuberculosis
in vivo and inhibits alpha Streptococcus, Diplococcus pneumoniae, and other gram-positive
bacteria in vitro. In addition, chelidonine also shows inhibitory effect on
Kauffman-Wolf Trichophyta and Epidermophyton floccosum .6. Other pharmacological effectsChelidonine showed protective effects on cadmium chloride-induced liver and
kidney 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 the
anaphylactic shock. In addition, chelidonine has anti-mite effect and good synergistic
effect with trichlorfon or omethoate to prevent cotton bollworm.
Clinical Use
Chelidonine has been used as a painkiller in clinical application due to its significant
analgesic effect. Chelidonine phosphate can be used for treatment of gastrointestinal
and ulcer pain, as a substitute of morphine preparations. Wei Tong Shu capsule
is used to treat pain caused by gastric convulsion, chronic gastritis, gastric ulcer, and
duodenal ulcer. Its main effective compositions are chelidonine and protopine. Fu
Fang Zhong Yao Tong An injection has collateral dredging and analgesic effects and
can be used for the treatment of moderate pain caused by chemoradiotherapy or
non-chemoradiotherapy of gastric cancer, lung cancer, and liver cancer. Its two
main components are chelidonine and sinomenine. Ukrain (NSC-631570), a phosphorothioate
derivative of chelidonine, has been used in clinical treatment as an
effective antitumor drug for the treatment of lung cancer, breast cancer, prostate
cancer, and pancreatic cancer.
Check Digit Verification of cas no
The CAS Registry Mumber 476-32-4 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 4,7 and 6 respectively; the second part has 2 digits, 3 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 476-32:
(5*4)+(4*7)+(3*6)+(2*3)+(1*2)=74
74 % 10 = 4
So 476-32-4 is a valid CAS Registry Number.
InChI:InChI=1/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
476-32-4Relevant academic research and scientific papers
Enantioselective Syntheses of Strychnos and Chelidonium Alkaloids through Regio- and Stereocontrolled Cooperative Catalysis
Fyfe, James W. B.,Hutchings-Goetz, Luke S.,Snaddon, Thomas N.,Yang, Chao
supporting information, p. 17556 - 17564 (2020/08/14)
We describe enantioselective syntheses of strychnos and chelidonium alkaloids. In the first case, indole acetic acid esters were established as excellent partner nucleophiles for enantioselective cooperative isothiourea/Pd catalyzed α-alkylation. This provides products containing indole-bearing stereocenters in high yield and with excellent levels of enantioinduction in a manner that is notably independent of the N-substituent. This led to concise syntheses of (?)-akuammicine and (?)-strychnine. In the second case, the poor performance of ortho-substituted cinnamyl electrophiles in the enantioselective cooperative isothiourea/Ir catalyzed α-alkylation was overcome by appropriate substituent choice, leading to enantioselective syntheses of (+)-chelidonine, (+)-norchelidonine, and (+)-chelamine.
Enantioselective synthesis of chelidonine, a B/C-cis-11- hydroxyhexahydrobenzo[c]phenanthridine alkaloid
Ito, Miki,Konno, Fujiko,Kumamoto, Takuya,Suzuki, Noriyuki,Kawahata, Masatoshi,Yamaguchi, Kentaro,Ishikawa, Tsutomu
experimental part, p. 8041 - 8049 (2011/11/12)
Both enantiomers of chelidonine, a B/C-cis-11-hydroxyhexahydrobenzo[c] phenanthridine alkaloid, were synthesized by manipulation of the B/C-dehydro ring juncture of benzo[c]phenanthridine skeleton using Sharpless asymmetric dihydroxylation and stereospecific catalytic hydrogenation after introduction of oxygen functions on the C ring as key reaction steps for the construction of stereogenic centers.
Concise enantioselective total syntheses of (+)-homochelidonine, (+)-chelamidine, (+)-chelidonine, (+)-chelamine and (+)-norchelidonine by a PdII-catalyzed ring-opening strategy
Fleming, Matthew J.,McManus, Helen A.,Rudolph, Alena,Chan, Walter H.,Ruiz, Jeremy,Dockendorff, Chris,Lautens, Mark
experimental part, p. 2112 - 2124 (2009/04/06)
New enantioselective syntheses of the B/C hexahydrobenzo[c]phenanthridine alkaloids (+)-homochelidonine, (+)-chelamidine, (+)-chelidonine, (+)-chelamine, and (+)-norchelidonine are described. Our rapid and convergent route to this class of natural products involved the development and application of a Pd II-catalyzed asymmetric ring-opening reaction of a mesoazabicyclic alkene with an aryl boronic acid as the key step. By screening a variety of functionalized ortho-substituted aryl boronic acids, chiral ligands and reaction conditions we were able to prepare the requisite cis-1-amino-2- aryldihydronaphthalenes in high yield and in up to 90% ee. Early attempts to complete the synthesis of (+)-homochelidonine using an N-Boc azabicyclic alkene are described in full. The successful route required a protecting group alteration followed by B ring for-mation and then stereoselective installation of the C-11 syn-hydroxy group by regioselective epoxide ring-opening using a hydride source. Ring-opening of the same epoxide intermediate with water ultimately led to the synthesis of (+)-chelamidine. The same strategy was then used to synthesize the other structurally similar B/C hexahydrobenzo[c] phenanthridine alkaloids, (+)-chelidonine, (+)-chelamidine, and (+)norchelidonine.
