ELLIPTICINE Chemical Properties

Melting point:

316-318°C

Boiling point:

379.31°C (rough estimate)

Density 

1.257±0.06 g/cm3 (20 ºC 760 Torr)

refractive index 

1.5794 (estimate)

storage temp. 

Keep in dark place,Sealed in dry,2-8°C

solubility 

DMSO: soluble

form 

Bright yellow solid

pka

16.59±0.40(Predicted)

Merck 

13,3581

LogP

4.800

CAS DataBase Reference

519-23-3(CAS DataBase Reference)

Safety Information

Hazard Codes 

T

Risk Statements 

25

Safety Statements 

45

RIDADR 

UN 3462 6.1/PG 3

WGK Germany 

3

RTECS 

UU8825000

HazardClass 

6.1(b)

PackingGroup 

III

Toxicity

LD50 in mice (mg/kg): 19.5-22.4 i.v.; 178-204 orally (Rakieten)

MSDS

• Language:English Provider:SigmaAldrich

ELLIPTICINE Usage And Synthesis

Description

Ellipticine is an alkaloid isolated from Apocyanaceae plants that exhibits antitumor activities by intercalating into DNA and/or inhibiting DNA topoisomerase II. It forms covalent adducts in DNA after being enzymatically activated with cytochrome P450 isoforms (e.g., CYP3A4, CYP1A1, or CYP1A2) or by peroxidases in target tissues. Ellipticine has been shown to inhibit the proliferation of 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 with IC₅₀ values ranging from 0.27-4.7 μM.

Uses

Ellipticine is a DNA intercalating agent and exhibits antitumor activities.

Definition

ChEBI: A organic heterotetracyclic compound that is pyrido[4,3-b]carbazole carrying two methyl substituents at positions 5 and 11.

Synthesis Reference(s)

Journal of the American Chemical Society, 102, p. 1457, 1980 DOI: 10.1021/ja00524a059
The Journal of Organic Chemistry, 72, p. 7106, 2007 DOI: 10.1021/jo070774z
Tetrahedron Letters, 18, p. 4663, 1977 DOI: 10.1016/S0040-4039(01)83595-4

General Description

A topoisomerase II inhibitor. Acts as an intercalative alkaloid that stimulates topoisomerase II-mediated DNA breakage. Is also capable of uncoupling mitochondrial oxidative phosphorylation.

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.

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