483-18-1 Usage
Description
Emetine hydrochloride (483-18-1) is one of the active ingredients of ipecac root extract, used as an emetic.1 Induces apoptosis in breast cancer cells via inhibition of Wnt/β-catenin signaling.2 Inhibits Zika and Ebola virus in vitro and in vivo, targeting viral entry and replication by inhibiting viral RNA polymerase and host lysosomal function.3 Also inhibits SARS-CoV-2 replication in cells (EC50 for viral load reduction is 0.46 μM).4 A useful agent for inhibiting protein synthesis in eukaryotic cells by virtue of its inhibition of the ribosome 40S subunit.5
Chemical Properties
Brown Solid
Uses
Different sources of media describe the Uses of 483-18-1 differently. You can refer to the following data:
1. Emetine is the principal alkaloid of ipecac, the ground roots of Uragoga ipecacuanha.
2. Emetine occurs in the ground roots ofipecac (Uragoga ipecacuanha, Cephaelisipecacuanha, Uragoga acuminata, and Rubiaceae). Ipecacs are of two varieties, Brazilianand Cartagena. The former contains about1.2–1.5% emetine, and the latter constitutesabout 1.1–1.4% emetine. It is used as anemetic to induce vomiting for the treatmentof poisoning. It is also used as an antiamebic.
Indications
Chlorprothixene (Taractan) has been reported twice to be effective in the
treatment of PHN. For severe pain, an initial 50 to 100 mg IM injection has
been advocated. Otherwise, the dosage is 25 to 50 mg PO q6h. The recommended
duration of therapy is 4 to 10 days. Higher doses are unwarranted and
frequently result in side effects.
Definition
ChEBI: A pyridoisoquinoline comprising emetam having methoxy substituents at the 6'-, 7'-, 10- and 11-positions.
Brand name
Asmorex;Broncho-tetracycline;Dicton-retard;Emedrin;Emetocamphrol;Hemometina;Optairosol;Pectinfant.
World Health Organization (WHO)
Emetine, an alkaloid obtained from ipecacuanha, was first used
rationally as an amoebocide in 1912. It was subsequently widely used and was
included in earlier editions of the WHO Model List of Essential Drugs but has now
been replaced by the less cardiotoxic synthetic derivative dehydroemetine.
Although it is valuable in the treatment of systemic amoebic hepatitis it has now
been largely superseded by considerably less toxic drugs, and in particular by
metronidazole.
Hazard
Toxic by ingestion.
Health Hazard
The toxicity of cephaeline is lower than thatof emetine. The toxic effects are cumulative. Ingestion of high doses may producehypotension, muscle weakness, and gastroin testinal problems, including nausea, vomit ing, and diarrhea.
Mechanism of action
This drug has a direct amebicidal effect against trophozoites E. histolytica in tissues, and
it is not active against cysts in either the lumen or intestinal walls, or in other organs.
The mechanism of action of emetine consists of the blockage of protein synthesis in
eukaryotic (but not in prokaryotic) cells. It inhibits the process of polypeptide chain
formation. Protein synthesis is inhibited in parasite and mammalian cells, but not in
bacteria.
Emetine is currently only used as a drug for treating amebiasis in cases of resistance to
other drugs. Synonyms of this drug are ipecin and methylcefalin.
Synthesis
Emetine, 3-ethyl-2,3,4,6,7,11b-hexahydro-9,10-dimethoxy-2-(1,2,3,4-tetrahydro-
6,7-dimethoxy-1-isoquinolylmethyl)-1H-benzo[a]quinolizine (37.2.8), is a natural compound. Traditionally, the alkaloid emetine was extracted from the ipecacuanha plant
(Brazilian root) and used as the primary drug for treating amebiasis, leishaniasis, and dysentery. Various ways of synthesizing emetine have been suggested, all of which begin with
homoveratrylamine – 2-(3,4-dimethoxyphenyl)ethylamine.
Upon a combined catalytic hydrogenation of the ethyl ester of β–(α′-cyano)propylglutaric acid and homoveratrilamine, a reductive amination reaction takes place, in which
ammonia is released and an intermediate amine (37.2.5) is formed, which under the reaction conditions undergoes intramolecular cyclization to give 1-[2-(3,4-dimethoxyphenyl)-
ethyl]-4-carbethoxymethyl-6-ethylpiperidone-2 (37.2.6). Reacting the resulting lactam
with phosphorus oxychloride causes heterocyclization into the derivative of benzoquinolizine (37.2.7). Subsequent reaction of the product with homoveratrylamine makes the corresponding amide. Upon reaction with phosphorus oxychloride, this compound cyclizes to
an isoquinoline derivative, and the pyridine ring is then hydrogenated by hydrogen to a
racemic mixture of products, from which the desired emetine is isolated.
References
1) Lee et al. (2008), Ipecacuanha: the South American vomiting root; J R Coll. Physicians Edinb., 38 355
2) Sun et al. (2019), Emetine Exhibits Anticancer Activity in Breast Cancer Cells as an Antagonist of Wnt/β-catenin Signaling; Oncol. Rep., 42 1735
3) Yang et al. (2018), Changing cancer survival in China during 2003-2015: a pooled analysis of 17 population-based cancer registries; Cell Discov., 4 31
4) Choy et al. (2020), Remdesivir, Lopinavir, and Homoharringtonine Inhibit SARS-CoV-2 Replication in Vitro; Antivir. Res., 178 104786
5) Cuyas et al. (2015), Anti-protozoal and Anti-Bacterial Antibiotics That Inhibit Protein Synthesis Kill Cancer Subtypes Enriched for Stem Cell-Like Properties; Cell Cycle, 14 3527
Check Digit Verification of cas no
The CAS Registry Mumber 483-18-1 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 4,8 and 3 respectively; the second part has 2 digits, 1 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 483-18:
(5*4)+(4*8)+(3*3)+(2*1)+(1*8)=71
71 % 10 = 1
So 483-18-1 is a valid CAS Registry Number.
InChI:InChI=1S/C29H40N2O4/c1-6-18-17-31-10-8-20-14-27(33-3)29(35-5)16-23(20)25(31)12-21(18)11-24-22-15-28(34-4)26(32-2)13-19(22)7-9-30-24/h13-16,18,21,24-25,30H,6-12,17H2,1-5H3
483-18-1Relevant articles and documents
A Cyclopeptide and a Tetrahydroisoquinoline Alkaloid from Ophiorrhiza nutans
Onozawa, Tadayoshi,Kitajima, Mariko,Kogure, Noriyuki,Peerakam, Nichakan,Santiarworn, Dammrong,Takayama, Hiromitsu
, p. 2156 - 2160 (2017/08/04)
A new cyclopeptide, ophiorrhisine A (1), a new tetrahydroisoquinoline alkaloid, 7′,10-dide-O-methylcephaeline (2), two known β-carboline alkaloids, and four known tetrahydroisoquinoline alkaloids were isolated from Ophiorrhiza nutans (Rubiaceae). Compound 1 is a tetrapeptide possessing a 14-membered paracyclophane ring and a novel N,N,N-trimethyltyrosine residue in the side chain. The stereochemistry at the aryl-alkyl ether bond was different from that of other known 14-membered paracyclophanes. The structure of 2 was established by spectroscopic analysis and semisynthesis.
Molecular cloning of an O-methyltransferase from adventitious roots of carapichea ipecacuanha
Cheong, Bo Eng,Takemura, Tomoya,Yoshimatsu, Kayo,Sato, Fumihiko
experimental part, p. 107 - 113 (2011/09/30)
Carapichea ipecacuanha produces various emetinetype alkaloids, known as ipecac alkaloids, which have long been used as expectorants, emetics, and amebicides. In this study, we isolated an O-methyltransferase cDNA from this medicinal plant. The encoded protein (CiOMT1) showed 98% sequence identity to IpeOMT2, which catalyzes the 7′-O-methylation of 7′-O- demethylcephaeline to form cephaeline at the penultimate step of emetine biosynthesis (Nomura and Kutchan, J. Biol. Chem., 285, 7722-7738 (2010)). Recombinant CiOMT1 showed both 7′-O-methylation and 6′-O-methylation activities at the last two steps of emetine biosynthesis. This indicates that small differences in amino acid residues are responsible for distinct regional methylation specificities between IpeOMT2 and CiOMT1, and that CiOMT1 might contribute to two sequential O-methylation steps from 7′-O- demethylcephaeline to emetine.
Formal total synthesis of (-)-emetine using catalytic asymmetric allylation of cyclic imines as a key step
Itoh, Takashi,Miyazaki, Michiko,Fukuoka, Hiromi,Nagata, Kazuhiro,Ohsawa, Akio
, p. 1295 - 1297 (2007/10/03)
Catalytic asymmetric allylation of 3,4-dihydro-6,7-dimethoxyisoquinoline was carried out using allyltrimethoxysilane in the presence of Cu(I) and tol-BINAP. The allyl adduct thus obtained was transformed to a chiral synthetic intermediate for (-)-emetine in good yield. The procedure was applied to the total synthesis of ent-emetine.
