Ellipticine

Ellipticine

Names
Preferred IUPAC name 5,11-Dimethyl-6H-pyrido[4,3-b]carbazole
Identifiers
CAS Number	519-23-3
3D model (JSmol)	Interactive image
ChEBI	CHEBI:4776
ChemSpider	3100
ECHA InfoCard	100.007.514
EC Number	208-264-0
KEGG	C09154
PubChem CID	3213
UNII	117VLW7484
CompTox Dashboard (EPA)	DTXSID30199855
InChI InChI=1S/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
SMILES CC1=C2C(=C(C3=C1C=CN=C3)C)C4=CC=CC=C4N2
Properties
Chemical formula	C17H14N2
Molar mass	246.313 g·mol−1
Appearance	Yellow solid
Density	1.257±0.06 g/cm3
Melting point	316–318 °C (601–604 °F; 589–591 K)
Solubility in water	Very low
Hazards
GHS labelling:
Pictograms
Hazard statements	H301
Precautionary statements	P264, P270, P301+P310, P321, P330, P405, P501
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Ellipticine is an alkaloid first extracted from trees of the species Ochrosia elliptica and Rauvolfia sandwicensis, which inhibits the enzyme topoisomerase II via intercalative binding to DNA.

Natural occurrence and synthesis

Ellipticine is an organic compound present in several trees within the genera Ochrosia, Rauvolfia, Aspidosperma, and Apocynaceae. It was first isolated from Ochrosia elliptica Labill., a flowering tree native to Australia and New Caledonia which gives the alkaloid its name, in 1959, and synthesised by Robert Burns Woodward later the same year.

Biological activity

Ellipticine is a known intercalator, capable of entering a DNA strand between base pairs. In its intercalated state, ellipticine binds strongly and lies parallel to the base pairs, increasing the superhelical density of the DNA. Intercalated ellipticine binds directly to topoisomerase II, an enzyme involved in DNA replication, inhibiting the enzyme and resulting in powerful antitumour activity. In clinical trials, ellipticine derivatives have been observed to induce remission of tumour growth, but are not used for medical purposes due to their high toxicity; side effects include nausea and vomiting, hypertension, cramp, pronounced fatigue, mouth dryness, and mycosis of the tongue and oesophagus.

Further DNA damage results from the formation of covalent DNA adducts following enzymatic activation of ellipticine by with cytochromes P450 and peroxidases, meaning that ellipticine is classified as a prodrug.