Ellipticine is an

alkaloid Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar ...

first extracted from trees of the species ''

Ochrosia elliptica ''Ochrosia elliptica'', known as elliptic yellowwood, bloodhorn or kopsia is a flowering tree native to north-eastern Australia, Lord Howe Island and New Caledonia. The tree bears an inedible red colored fruit with a white sticky flesh. It has b ...

'' and ''

Rauvolfia sandwicensis ''Rauvolfia sandwicensis'', the devil's-pepper, also known as ''hao'' in the Hawaiian language, is a species of flowering plant in the milkweed family, Apocynaceae, that is endemic to Hawaii. It is a shrub, a small tree In botany, a t ...

'', which inhibits the enzyme topoisomerase II via intercalative binding to DNA.

Natural occurrence and synthesis

Ellipticine is an

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The ...

present in several trees within the genera '' Ochrosia'', ''

Rauvolfia ''Rauvolfia'' (sometimes spelled ''Rauwolfia'') is a genus of evergreen trees and shrubs, commonly known as devil peppers, in the family Apocynaceae. The genus is named to honor Leonhard Rauwolf. The genus can mainly be found in tropical reg ...

'', ''

Aspidosperma ''Aspidosperma'' is a genus of flowering plant in the family Apocynaceae, first described as a genus in 1824. It is native to South America, Central America, southern Mexico, and the West Indies The West Indies is a subregion of North A ...

'', and ''

Apocynaceae Apocynaceae (from ''Apocynum'', Greek for "dog-away") is a family of flowering plants that includes trees, shrubs, herbs, stem succulents, and vines, commonly known as the dogbane family, because some taxa were used as dog poison Members of the ...

''. It was first isolated from ''

'' Labill., a flowering tree native to

Australia Australia, officially the Commonwealth of Australia, is a Sovereign state, sovereign country comprising the mainland of the Australia (continent), Australian continent, the island of Tasmania, and numerous List of islands of Australia, sma ...

and

New Caledonia ) , anthem = "" , image_map = New Caledonia on the globe (small islands magnified) (Polynesia centered).svg , map_alt = Location of New Caledonia , map_caption = Location of New Caledonia , mapsize = 290px , subdivision_type = Sovereign st ...

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 Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

involved in

DNA replication In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all living organisms acting as the most essential part for biological inheritanc ...

, inhibiting the enzyme and resulting in powerful antitumour activity. In clinical trials, ellipticine derivatives have been observed to induce remission of

tumour A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

growth, but are not used for medical purposes due to their high

toxicity Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subst ...

; side effects include

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

and

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose. Vomiting can be the result of ailments like Food-poisoning, foo ...

hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...

, cramp, pronounced

fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...

, mouth dryness, and mycosis of the tongue and

oesophagus The esophagus (American English) or oesophagus (British English; both ), non-technically known also as the food pipe or gullet, is an organ in vertebrates through which food passes, aided by peristaltic contractions, from the pharynx to the ...

. Further DNA damage results from the formation of covalent DNA adducts following enzymatic activation of ellipticine by with

cytochrome Cytochromes are redox-active proteins containing a heme, with a central Fe atom at its core, as a cofactor. They are involved in electron transport chain and redox catalysis. They are classified according to the type of heme and its mode of bin ...

s P450 and peroxidases, meaning that ellipticine is classified as a

prodrug A prodrug is a medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be used to improve how the drug ...

References

{{reflist Indole alkaloids Isoquinoline alkaloids Carbazoles Heterocyclic compounds with 4 rings Nitrogen heterocycles DNA replication inhibitors Prodrugs Topoisomerase inhibitors DNA intercalaters Plant toxins