315-22-0 Usage
Description
Monocrotaline (MCT) is a toxic 11-membered macrocyclic pyrrolizidine alkaloid (PA) derived from the seeds of the Crotalaria spectabilis plant. It is known for its hepatotoxic properties and is used as a primary reference substance with assigned absolute purity. It is also used in research for inducing pulmonary diseases and hypertension in experimental animals.
Uses
1. Antineoplastic Applications:
Monocrotaline is used as an antineoplastic agent, particularly for inducing pulmonary diseases in rats. It is also used in hydrochloric acid (HCl) and injected into experimental animals to induce pulmonary hypertension, which helps in the study of human pulmonary hypertension.
2. Insect Sterilant:
Monocrotaline is used as an insect sterilant, contributing to pest control and management.
3. Research and Development:
Monocrotaline is produced for research use, specifically in the development of rat models to investigate human pulmonary hypertension. It offers technical simplicity, reproducibility, and low cost compared with other models of pulmonary hypertension.
4. Pharmaceutical Applications:
Monocrotaline is used in the pharmaceutical industry for its hepatotoxic properties, which can be utilized in the development of drugs targeting liver-related conditions.
5. Toxicological Studies:
Monocrotaline is used in toxicological studies to understand the effects of pyrrolizidine alkaloids on human and animal health, as well as to develop strategies for detoxification and prevention of poisoning.
Physical Properties:
Appearance: White prism crystal
Solubility: Soluble in methanol, ethanol, and chloroform; slightly soluble in benzene, water, ether, and acetone; insoluble in petroleum ether
Melting Point: 197–198 °C
Specific Optical Rotation: -54.7° (in chloroform)
References
[1] Jose G. Gomez-Arroyo, Laszlo Farkas, Aysar A. Alhussaini, Daniela Farkas, Donatas Kraskauskas, Norbert F. Voelkel, Harm J. Bogaard (2012) The monocrotaline model of pulmonary hypertension in perspective, Am J Physio Lung Cell Mol Phyisol, 302, L363-L369
[2] https://pubchem.ncbi.nlm.nih.gov/compound/monocrotaline#section=Top
References
Adams, Rogers., J. Amer. Chern. Soc., 61,2815 (1939)
History
In 1935, W.?M. Neil and L.?L. Russoff isolated monocrotaline from Crotalaria sessiliflora L.?Monocrotaline showed anticancer activity in?vivo, especially for treating squamous cell carcinoma, cervical cancer, and leukemia. However, since many pyrrolizidine alkaloid compounds have hepatotoxicity, further development of these compounds is restricted.China began the research of monocrotaline, as early as 1943. Crotalaria sessiliflora L. was also recorded in the 1977 edition of the Pharmacopoeia of the People’s Republic of China. But monocrotaline was reported for its liver toxicity; teratogenic,
allergic reactions; and other side effects, limiting its further clinical applications. In
1992, the Ministry of Health stopped the clinical application of monocrotaline injection. Further pharmacology study is essential for monocrotaline .
Indications
This product is available in the Pharmacopoeia of the People’s Republic of China (1977).Clinical available formulations include gel and liposome transdermal preparations. It is effective in treating skin cancer, basal cell carcinoma, acute leukemia,
and cervical and penile cancer.
Biochem/physiol Actions
Crotaline induces pulmonary vascular syndrome in rats. It is considered toxic and results in hepatic cirrhosis, enlarged liver, sinusoidal obstruction syndrome and right ventricular hypertrophy.
Pharmacology
Monocrotaline is a pyrrolizidine alkaloid which has anticancer and anti-choline effects. In vitro study suggested that monocrotaline has significant cytotoxicity in human BEL-7402, KB cancer cells through inducing DNA alkylation . Monocrotaline’s toxicity is low, but its metabolites in the liver have high liver toxicity. The metabolites are highly electrophilic and can bind to enzymes, proteins, DNA, and RNA, thus causing several side effects. Monocrotaline can reduce blood pressure and inhibit cardiac contractility and heart rate and also shows mild inhibition of respiratory rate and depth.
Clinical Use
Monocrotaline injection shows well therapeutic effect for treating squamous cell carcinoma and basal cell carcinoma. In folk, the fresh pulp or dry powder of the herb has been also used for treating squamous cell carcinoma and basal cell carcinoma .
Safety Profile
Suspected carcinogen
with experimental carcinogenic data. Poison
by ingestion, intravenous, intraperitoneal,
and subcutaneous routes. Human mutation
data reported. When heated to
decomposition it emits toxic fumes of NOx.
Purification Methods
Crotaline forms prisms from absolute EtOH and recrystallises also from CHCl3. UV in 96% EtOH has max 217nm (log 3.32). [Adams et al. J Am Chem Soc 74 5612 1952, Culvenor & Smith Aust J Chem 10 474 1957.] The hydrochloride has m 212-214o (from MeOH/Et2O) and [] D28 -38.4o (c 5, H2O) [Adams & Gianturco J Am Chem Soc 78 1922 1956]. The picrate has m 230-231.5o(dec) [Adams et al. J Am Chem Soc 74 5614 1952]. [Beilstein 27 III/IV 6660.]
Check Digit Verification of cas no
The CAS Registry Mumber 315-22-0 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 3,1 and 5 respectively; the second part has 2 digits, 2 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 315-22:
(5*3)+(4*1)+(3*5)+(2*2)+(1*2)=40
40 % 10 = 0
So 315-22-0 is a valid CAS Registry Number.
InChI:InChI=1/C16H23NO6/c1-9-13(18)23-11-5-7-17-6-4-10(12(11)17)8-22-14(19)16(3,21)15(9,2)20/h4,9,11-12,20-21H,5-8H2,1-3H3/p+1/t9-,11+,12+,15+,16-/m0/s1
315-22-0Relevant articles and documents
Human intestinal bacteria mediate reduction of the N-oxides of isoline and monocrotaline to the corresponding parent alkaloids
Tang, Jun,Wang, Zhengtao,Akao, Teruaki,Hattori, Masao
, p. 2027 - 2030 (2013)
The role of human intestinal bacteria in the biotransformation of pyrrolizidine alkaloid N-oxides was investigated. Two naturally-occurring hepatotoxic pyrrolizidine alkaloids, isoline and monocrotaline and their N-oxides were incubated with a human fecal suspension in an in vitro model, respectively. The metabolites were isolated and purified by chromatographic techniques and identified by the spectral analyses and the metabolic profiles were further analyzed by a specific TLC method. Human intestinal bacteria showed high reduction effects on the pyrrolizidine alkaloid N-oxides but not on the resultant tertiary alkaloids, suggesting that IB may play a partial role in the cyclic conversion between each pyrrolizidine alkaloid and its N-oxide in vivo. This evidence implied the potential risk of the pyrrolizidine alkaloid-containing Chinese medicinal herbs to human health when used in decoctions.
TOTAL SYNTHESIS OF OPTICALLY ACTIVE MONOCROTALINE, A CARCINOGENIC PYRROLIZIDINE ALKALOID HAVING AN 11-MEMBERED DILACTONE
Niwa, Haruki,Okamoto, Osamu,Yamada, Kiyoyuki
, p. 5139 - 5142 (2007/10/02)
Monocrotaline (1), a representative of carcinogenic pyrrolizidine alkaloids with an 11-membered dilactone has been synthesized in optically active form by virtue of regioselective coupling of (+)-retronecine (2) and the protected necic acid 3, the latter being synthesized enantioselectively from the meso-diester 4.