Acetogenins are a class of

polyketide Polyketides are a class of natural products derived from a precursor molecule consisting of a chain of alternating ketone (or reduced forms of a ketone) and methylene groups: (-CO-CH2-). First studied in the early 20th century, discovery, biosynth ...

natural product A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical syn ...

s found in plants of the family

Annonaceae The Annonaceae are a Family (biology), family of flowering plants consisting of trees, shrubs, or rarely lianas commonly known as the custard apple family or soursop family. With 108 accepted genera and about 2400 known species, it is the largest ...

. They are characterized by linear 32- or 34-carbon chains containing oxygenated functional groups including

hydroxyl In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy ...

ketone In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double bo ...

epoxide In organic chemistry, an epoxide is a cyclic ether () with a three-atom ring. This ring approximates an equilateral triangle, which makes it strained, and hence highly reactive, more so than other ethers. They are produced on a large scale for ...

tetrahydrofuran Tetrahydrofuran (THF), or oxolane, is an organic compound with the formula (CH2)4O. The compound is classified as heterocyclic compound, specifically a cyclic ether. It is a colorless, water-miscible organic liquid with low viscosity. It is ma ...

s and

tetrahydropyran Tetrahydropyran (THP) is the organic compound consisting of a saturated six-membered ring containing five carbon atoms and one oxygen atom. It is named by reference to pyran, which contains two double bonds, and may be produced from it by addi ...

s. They are often terminated with a

lactone Lactones are cyclic carboxylic esters, containing a 1-oxacycloalkan-2-one structure (), or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring. Lactones are formed by intramolecular esterification of the co ...

butenolide Butenolides are a class of lactones with a four-carbon heterocyclic ring structure.Joule JA, Mills K. (2000). Heterocyclic Chemistry 4th ed. Blackwell Science Publishing: Oxford, UK They are sometimes considered oxidized derivatives of furan. The ...

. Over 400 members of this family of compounds have been isolated from 51 different species of plants. Many acetogenins are characterized by

neurotoxicity Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specificall ...

. Examples include: *

Annonacin Annonacin is a chemical compound with toxic effects, especially in the nervous system, found in some fruits such as the paw paw, custard apples, soursop, and others from the family ''Annonaceae''. It is a member of the class of compounds known ...

Annonin Annonins are a group of chemical compounds classified as acetogenins. They are found in the extracts of ''Annona'' seeds ('' A. squamosa'' and '' A. muricata''). Annonin-based bioinsecticides are used to control Coleoptera (beetle) pests commonl ...

s *

Bullatacin Bullatacin is a bis(tetrahydrofuranoid) fatty acid lactone found in some fruits from Annonaceae family. It is a member of the class of compounds known as acetogenin Acetogenins are a class of polyketide natural products found in plants of the f ...

Uvaricin Uvaricin is a bis(tetrahydrofuranoid) fatty acid lactone that was first isolated in 1982 from the roots of the Annonaceae ''Uvaria acuminata''. Uvaricin was the first known example in a class of compounds known as acetogenins. Acetogenins, which ar ...

Structure

Structurally, acetogenins are a series of C-35/C-37 compounds usually characterized by a long

aliphatic In organic chemistry, hydrocarbons ( compounds composed solely of carbon and hydrogen) are divided into two classes: aromatic compounds and aliphatic compounds (; G. ''aleiphar'', fat, oil). Aliphatic compounds can be saturated, like hexane, or ...

chain bearing a terminal methyl-substituted α,β-unsaturated γ-lactone ring, as well as one to three tetrahydrofuran (THF) rings. These THF rings are located along the

hydrocarbon In organic chemistry, a hydrocarbon is an organic compound consisting entirely of hydrogen and carbon. Hydrocarbons are examples of group 14 hydrides. Hydrocarbons are generally colourless and hydrophobic, and their odors are usually weak or ex ...

chain, along with a number of oxygenated moieties (hydroxyls,

acetoxy In organic chemistry, the acetoxy group (abbr. AcO or OAc; IUPAC name: acetyloxy), is a functional group with the formula and the structure . As the ''-oxy'' suffix implies, it differs from the acetyl group () by the presence of an additio ...

ls, ketones, epoxides) and/or double bonds.

Research

Acetogenins have been investigated for their biological properties, but are a concern due to

. Purified acetogenins and crude

extract An extract is a substance made by extracting a part of a raw material, often by using a solvent such as ethanol, oil or water. Extracts may be sold as tinctures, absolutes or in powder form. The aromatic principles of many spices, nuts, h ...

s of the common North American pawpaw (''

Asimina triloba ''Asimina triloba'', the American papaw, pawpaw, paw paw, or paw-paw, among many regional names, is a small deciduous tree native to the eastern United States and Canada, producing a large, yellowish-green to brown fruit. ''Asimina'' is the onl ...

'') or the soursop ('' Annona muricata'') remain under laboratory studies.

Mechanism of action

Acetogenins inhibit

NADH dehydrogenase NADH dehydrogenase is an enzyme that converts nicotinamide adenine dinucleotide (NAD) from its reduced form (NADH) to its oxidized form (NAD+). Members of the NADH dehydrogenase family and analogues are commonly systematically named using the for ...

, a key enzyme in energy metabolism.

References

External links

* {{commonscat-inline, Acetogenins Fatty alcohols Polyketides NADH dehydrogenase inhibitors Plant toxins