519-23-3 Usage
Description
Ellipticine is an organic heterotetracyclic compound, specifically a pyrido[4,3-b]carbazole with two methyl substituents at positions 5 and 11. It is an alkaloid derived from Apocyanaceae plants and is known for its antitumor activities. Ellipticine works by intercalating into DNA and inhibiting DNA topoisomerase II, leading to the formation of covalent adducts in DNA after enzymatic activation. ELLIPTICINE has demonstrated the ability to inhibit the proliferation of various cancer cell lines, including human breast adenocarcinoma, leukemia, neuroblastoma, and glioblastoma cells.
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.
Check Digit Verification of cas no
The CAS Registry Mumber 519-23-3 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 5,1 and 9 respectively; the second part has 2 digits, 2 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 519-23:
(5*5)+(4*1)+(3*9)+(2*2)+(1*3)=63
63 % 10 = 3
So 519-23-3 is a valid CAS Registry Number.
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
519-23-3Relevant articles and documents
Oxazoles in organic chemistry. Synthesis of the antitumor agent ellipticine
Kozikowski,Hasan
, p. 2039 - 2040 (1977)
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Cosson,J.P.,Schmid,M.
, p. 1353 - 1354 (1970)
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Exploiting an intramolecular Diels-Alder cyclization/dehydro-aromatization sequence for the total syntheses of ellipticines and calothrixin B
Deng, Chengdan,Liu, Yuancui,Xu, Mei,Xie, Kaiqiang,Liu, Sheng
, p. 1395 - 1403 (2021)
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
Castro, Joaquim A. M.,Ligiéro, Carolina B. P.,Maior, Christian R. S.,Miranda, Paulo C. M. L.,Morgon, Nelson H.,Naciuk, Fabrício F.,Rocco, Silvana A.,Serikava, Bruno K.
, (2022/03/02)
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.
Synthesis and cytotoxicity of novel bisellipticines and bisisoellipticines
Obaza-Nutaitis, Judy A.,Gribble, Gordon W.
, p. 171 - 187 (2019/07/31)
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).
