Ellipticine

Ellipticine is an organic compound present in several trees within the genera Ochrosia, Rauvolfia, and Aspidosperma.^[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]

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]