519-23-3

Basic information

• Product Name: ELLIPTICINE
• Synonyms: 5,11-DIMETHYLPYRIDO[4,3-B]CARBAZOLE;5,11-DIMETHYLPYRIDO[4.3:B]CARBAZOLE;5,11-DIMETHYL-6H-PYRIDO[4,3-B]CARBAZOLE;ELLIPTICINE;3-b)carbazole,5,11-dimethyl-6h-pyrido(;icig770;ELLIPTICINE, FOR FLUORESCENCE;ELLIPTICINE(RG)
• CAS NO: 519-23-3
• Molecular Formula: C₁₇H₁₄N₂
• Molecular Weight: 246.31
• EINECS: 208-264-0
• Product Categories: Alkaloids;Indoles and derivatives;Antitumour;Inhibitors
• Mol File: 519-23-3.mol

Chemical Properties

• Melting Point: 316-318°C
• Boiling Point: 379.31°C (rough estimate)
• Flash Point: 227.1°C
• Appearance: /
• Density: 1.257±0.06 g/cm3 (20 ºC 760 Torr)
• Vapor Pressure: 1.81E-09mmHg at 25°C
• Refractive Index: 1.5794 (estimate)
• Storage Temp.: 2-8°C
• Solubility: DMSO: soluble
• PKA: 16.59±0.40(Predicted)
• Merck: 13,3581
• CAS DataBase Reference: ELLIPTICINE(CAS DataBase Reference)
• NIST Chemistry Reference: ELLIPTICINE(519-23-3)
• EPA Substance Registry System: ELLIPTICINE(519-23-3)

Safety Data

• Hazard Codes: T
• Statements: 25
• Safety Statements: 45
• RIDADR: UN 3462 6.1/PG 3
• WGK Germany: 3
• RTECS: UU8825000
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 519-23-3(Hazardous Substances Data)

Usage

Uses

Used in Anticancer Applications:
Ellipticine is used as an anticancer agent for its ability to inhibit the proliferation of various cancer cell lines. It is particularly effective against human breast adenocarcinoma MCF-7 cells, leukemia HL-60 and CCRF-CEM cells, neuroblastoma IMR-32, UKF-NB-3, and UKF-NB-4 cells, and U87MG glioblastoma cells. ELLIPTICINE acts as a topoisomerase II inhibitor and an intercalative alkaloid, stimulating topoisomerase II-mediated DNA breakage and inhibiting cancer cell growth.
Used in Pharmaceutical Industry:
Ellipticine is used as a research compound in the pharmaceutical industry for its potential applications in developing new cancer treatments. Its unique mechanism of action, involving DNA intercalation and topoisomerase II inhibition, makes it a valuable tool for studying the molecular mechanisms of cancer and for designing novel therapeutic strategies.
Used in Drug Development:
Ellipticine is used as a lead compound in drug development, as its chemical structure and biological activities provide a foundation for the synthesis of new derivatives with improved pharmacological properties. These derivatives may exhibit enhanced antitumor activity, reduced toxicity, or better pharmacokinetic profiles, ultimately leading to the development of more effective cancer treatments.

Synthesis Reference(s)

Journal of the American Chemical Society, 102, p. 1457, 1980 DOI: 10.1021/ja00524a059The Journal of Organic Chemistry, 72, p. 7106, 2007 DOI: 10.1021/jo070774zTetrahedron Letters, 18, p. 4663, 1977 DOI: 10.1016/S0040-4039(01)83595-4

Biochem/physiol Actions

Cell permeable: yes

in vitro

treatment mammalian dna topoisomerase ii reaction mixture with ellipticine resulted in the stimulation of dna cleavage. the drug-stimulation of dna cleavage is related to the formation of a ternary complex between topoisomerase ii, dna, and ellipticine. ellipticine dose not inhibit enzyme-mediated dna religation, however, it stimulates dna breakage by enhancing the forward rate of cleavage [2]. ellipticine showed growth inhibition activity on l1210 lymphocytic leukemia cells with a ic50 of 0.99 μm [1].

in vivo

ellipticine was evaluated in p. berghei infected mice in the 4-day suppressive test. ellipticine had a 100% inhibition versus controls on days 5 and 7 at an oral dose of 50 mg/kg/day, and the mean survival time (mst) was more than 40 days [3].

IC 50

= 0.99 μm for l1210 lymphocytic leukemia cells [1]

Purification Methods

This DNA intercalator is purified by recrystallisation from CHCl3 or MeOH and is dried in vacuo. The UV max values in aqueous EtOH/HCl are at 241, 249, 307, 335 and 426nm. [Marini-Bettolo & Schmutz Helv Chim Acta 42 2146 1959.] The methiodide has m 360o(dec), with UV (EtOH/KOH) at 223, 242, 251, 311, 362 and 432nm. [Goodwin et al. J Am max Chem Soc 81 1903 1959, Beilstein 23/9 V 417.]

references

[1] paoletti c, cros s, xuong nd, lecointe p, moisand a. comparative cytotoxic and antitumoral effects of ellipticine derivatives on mouse l 1210 leukemia. chem biol interact. 1979 apr;25(1):45-58.[2] tewey km, chen gl, nelson em, liu lf. intercalative antitumor drugs interfere with the breakage-reunion reaction of mammalian dna topoisomerase ii. j biol chem. 1984 jul 25;259(14):9182-7.[3] rocha e silva lf, montoia a, amorim rc, melo mr, henrique mc, nunomura sm, costa mr, andrade neto vf, costa ds, dantas g, lavrado j, moreira r, paulo a, pinto ac, tadei wp, zacardi rs, eberlin mn, pohlit am. comparative in vitro and in vivo antimalarial activity of the indole alkaloids ellipticine, olivacine, cryptolepine and a synthetic cryptolepine analog. phytomedicine. 2012 dec 15;20(1):71-6.

InChI:InChI=1/C17H14N2/c1-10-14-9-18-8-7-12(14)11(2)17-16(10)13-5-3-4-6-15(13)19-17/h3-9,19H,1-2H3

Upstream product

• 114792-05-1 1-[1-acetyl-3-(1,1-di-indol-3-yl-ethyl)-1,4-dihydro-[4]pyridyl]-ethanone 
• 128773-76-2 2-(p-methoxbenzyl)-1,2,3,4-tetrahydro-5,11-dimethylpyrido<4,3-b>carbazole 
• 917-54-4 methyllithium 
• 137664-25-6 5-hydroxy-5-methyl-indolo<1,2-b><2,7>naphthyridin-12-one 
• 137664-27-8 1-(1H-indol-2-yl)-1-methyl-furo<3,4-c>pyridine-3(1H)-one 
• 73540-73-5 6-(methoxymethyl)-6H-pyrido[4,3-b]carbazole-5,11-dione 
• 73540-74-6 6-benzyl-5H-pyrido[4,3-b]carbazole-5,11(6H)-dione 
• 74606-36-3 6-benzyl-5,11-dimethyl-6H-pyrido[4,3-b]carbazole 
• 66604-68-0 2,5,11-trimethyl-6H-pyrido[4,3-b]carbazol-2-ium iodide 
• 90605-57-5 formaldehyde diethylmercaptal lithium salt 
• 137683-84-2 5-hydroxy-5-trimethylsilyloxy-indolo<1,2-b><2,7>naphthyridin-12-one 
• 93772-11-3 1,4-dimethylpyrano<3,4-b>indol-3-one 
• 93772-12-4 3-(3',3'-dimethyltriazene-1-yl)pyridine-4-carboxylic acid 
• 83402-10-2 2-<1-<4-(3-ethyl)pyridyl>>ethenylindole 

Downstream Products

• 74606-36-3 6-benzyl-5,11-dimethyl-6H-pyrido[4,3-b]carbazole 
• 74606-37-4 2-benzoyl-1-cyano-1,2-dihydroellipticine 
• 85619-20-1 2-Benzenesulfonyl-5,11-dimethyl-2,6-dihydro-1H-pyrido[4,3-b]carbazole-1-carbonitrile 
• 18073-33-1 6-methylellipticine 
• 77251-57-1 11-methyl-6H-pyrido<4,3-b>carbazole-5-carbaldehyde 
• 37687-33-5 ellipticine-N²-oxide 
• 18073-34-2 9-bromoellipticine 
• 18073-35-3 nitro-9 ellipticine 
• 108320-78-1 5-(hydroxymethyl)-11-methyl-6H-pyrido<4,3-b>carbazole 
• 51131-85-2 9-hydroxyellipticine 
• 110674-88-9 6-methyl-1,2-dihydroellipticin-1-one 
• 110689-74-2 2-acetyl-6-methyl-1,2-dihydroellipticin-1-one 
• 110674-90-3 11-<2-(2,3,5-tribenzoyl-β-D-ribofuranos-1-yl)oxyethyl>-5,6-dimethyl-pyrido<4,3-b>-carbazole 
• 85619-08-5 1-(p-bromobenzyl)-1,2,3,4-tetrahydroellipticine 

Relevant articles and documents

Chemistry of 6H-Pyridocarbazoles. Part 10 - Carbon-13 Nuclear Magnetic Resonance Spectra of Ellipticines and some Model Compounds

The 13C NMR spectrum of ellipticine has been re-interpreted by reference to model compounds, and correlated with the spectra of a number of new ellipticine derivatives.

Exploiting an intramolecular Diels-Alder cyclization/dehydro-aromatization sequence for the total syntheses of ellipticines and calothrixin B

The tetracyclic and pentacyclic skeletons of pyrido and quinolinocarbazole alkaloids have been synthesizedviaa unified strategy. The prominent key step involved a Diels-Alder intramolecular cyclization/dehydro-aromatization sequence. From these carbazole-lactam cores, linear syntheses have been developed for ellipticines and calothrixin B.

Regioselection Switch in Nucleophilic Addition to Isoquinolinequinones: Mechanism and Origin of the Regioselectivity in the Total Synthesis of Ellipticine

Ellipticine was synthesized in six steps and 20% global yield starting from the readily available 2,5-dimethoxy isoquinoline. Unprecedented regioselective control of the nucleophilic attack on the isoquinoline-5,8-dione is first described. Investigation of the possible pathways of this transformation through density functional theory calculations reveals unexpected N-oxide assistance in cascade tautomerizations, which was crucial for directing the nucleophilic attack and hastening the overall process. Using this strategy, we prepared the aniline-isoquinolinedione adduct and submitted it to an intramolecular double C-H cross-coupling activation to furnish ellipticinequinone, which gave ellipticine after a MeLi addition/BH3reduction sequence.

Simple method for preparing ellipticine or substituted ellipticine

The invention relates to a synthesis process for preparing ellipticine. Ellipticine is obtained through six steps of reaction and three steps of crystallization separation, the target product total yield is high, column chromatography separation is not needed for an intermediate product and the target product, and the method is particularly suitable for large-scale preparation.

Total Synthesis of Olivacine and Ellipticine via a Lactone Ring-Opening and Aromatization Cascade

Effective preparation of olivacine and ellipticine via late-stage D-ring cyclization is described. Key features of the synthetic routes include trifluoroacetic acid-mediated formation of a lactone that is fused to a tetrahydrocarbazole derivative and its one-pot two-step ring opening and aromatization mediated by para-toluenesulfonic acid and palladium on carbon, respectively.

Synthesis and cytotoxicity of novel bisellipticines and bisisoellipticines

A series of bis-ellipticines 7-9 and bis-isoellipticines 10-12 tethered through the indole nitrogen was synthesized and screened for antitumor cytotoxicity in the L-1210 murine leukemia assay. Activity was only displayed by 1,10-bis(6-ellipticinyl)-?-decane (8).

Regioexhaustive Functionalization of the Carbocyclic Core of Isoquinoline: Concise Synthesis of Oxoaporphine Core and Ellipticine

A general and versatile strategy has been developed for the functionalization of the carbocyclic core of the isoquinoline. This regioexhaustive approach employs electrophilic halogenation as a toolbox methodology and delivers highly decorated intermediates that can be further elaborated toward medicinally relevant building blocks or natural products.

Synthesis and in vitro antitumor activity of 9-hydroxyellipticine derivatives with glucose conjugation via triazolylmethyl succinate linker

Three types of novel 9-hydroxyellipticine derivatives 7a-c with glucose conjugation, linked by a triazolylmethyl succinic ester bond, were synthesized, and their cytotoxicity against HeLa S-3 and 293T cells was evaluated together with ellipticine (1) and 9-hydroxyellipticine (3). These new compounds 7a-c exhibited potent antitumor activity against HeLa S-3 and 293T, and water solubility of 7a was greatly higher than those of 1 and 3. The effects of an -OCH2CH2-spacer and the amino sugar moiety on the antitumor activity were examined using 7b,c. Furthermore, one of these glucose-conjugates 7a was applied to hydrolysis, catalyzed by carboxyesterase, leading to the formation of 3 under physiological conditions.

SMALL MOLECULES TARGETING REPEAT r(CGG) SEQUENCES

The invention provides a series of bioactive small molecules that target expanded r(CGG) repeats, termed r(CGG)exp, that causes Fragile X-associated Tremor Ataxia Syndrome (FXTAS). The compound was identified by using information on the chemotypes and RNA motifs that interact. Specifically, 9-hydroxy-5,11-dimethyl-2-(2-(piperidin-1-yl)ethyl)-6H-pyrido[4,3-b]carbazol-2-ium, binds the 5′CG/3′GGC motifs in r(CGG)exp and disrupts a toxic r(CGG)exp-protein complex. Specifically, dimeric compounds incorporating two 9-hydroxyellipticine analog structures can even more potently bind the 5′CGG/3′GGC motifs in r(CGG)exp and disrupts a toxic r(CGG)exp-protein complex. Structure-activity relationships (SAR) studies determined that the alkylated pyridyl and phenolic side chains are important chemotypes that drive molecular recognition of r(CGG) repeats, such as r(CGG)exp. Importantly, the compound is efficacious in FXTAS model cellular systems as evidenced by its ability to improve FXTAS-associated pre-mRNA splicing defects and to reduce the size and number of r(CGG)exp-protein aggregates.

Friedel-crafts cyclodehydration approach toward the synthesis of ellipti-cine and 9-methoxyellipticine

An expedient synthesis of biologically important pyrido[4,3-b]carbazole alkaloids, ellipticine and 9-methoxyellipticine, is reported. Our synthetic approach applies a key H3PO4-mediated Friedel-Crafts cyclodehydration to construct the pyridine core.