Ellipticine

Ellipticine is a tetracyclic alkaloid first extracted from trees of the species Ochrosia elliptica and Rauvolfia sandwicensis,^[5][6] which inhibits the enzyme topoisomerase II via intercalative binding to DNA.^[7]

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 crystalline powder[1]
Density	1.257±0.06 g/cm3[2]
Melting point	316–318 °C (601–604 °F; 589–591 K)[2]
Solubility in water	Very low[3]
Hazards
Occupational safety and health (OHS/OSH):
Main hazards	toxic
GHS labelling:
Pictograms	[4]
Hazard statements	H301[4]
Precautionary statements	P264, P270, P301+P310, P321, P330, P405, P501[4]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

Natural occurrence and synthesis

Ellipticine is an organic compound present in several trees within the genera Ochrosia, Rauvolfia, Aspidosperma, and Apocynaceae.^[8] 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,^[5] and synthesised by Robert Burns Woodward later the same year.^[6]

Biological activity

Ellipticine is a known intercalator, capable of entering a DNA strand between base pairs. In its intercalated state, ellipticine binds strongly^[9] and lies parallel to the base pairs,^[10] increasing the superhelical density of the DNA.^[11] Intercalated ellipticine binds directly to topoisomerase II, an enzyme involved in DNA replication,^[12] inhibiting the enzyme and resulting in powerful antitumour activity.^[10] 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.^[13]

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.^[14]