Английская Википедия:Ellipticine

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Ellipticine is an alkaloid first extracted from trees of the species Ochrosia elliptica and Rauvolfia sandwicensis,[1][2] which inhibits the enzyme topoisomerase II via intercalative binding to DNA.[3]

Natural occurrence and synthesis

Ellipticine is an organic compound present in several trees within the genera Ochrosia, Rauvolfia, Aspidosperma, and Apocynaceae.[4] 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,[1] and synthesised by Robert Burns Woodward later the same year.[2]

Biological activity

Ellipticine is a known intercalator, capable of entering a DNA strand between base pairs. In its intercalated state, ellipticine binds strongly[5] and lies parallel to the base pairs,[6] increasing the superhelical density of the DNA.[7] Intercalated ellipticine binds directly to topoisomerase II, an enzyme involved in DNA replication,[8] inhibiting the enzyme and resulting in powerful antitumour activity.[6] 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.[9]

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.[10]

References

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