acetogenin
{{short description|Group of chemical compounds}}
{{Distinguish|Acetogen}}
Acetogenins are a class of polyketide natural products found in plants of the family Annonaceae. They are characterized by linear 32- or 34-carbon chains containing oxygenated functional groups including hydroxyls, ketones, epoxides, tetrahydrofurans and tetrahydropyrans. They are often terminated with a lactone or butenolide.{{cite journal | last1 = Li | first1 = N. | last2 = Shi | first2 = Z. | last3 = Tang | first3 = Y. | last4 = Chen | first4 = J. | last5 = Li | first5 = X. | title = Recent Progress on the Total Synthesis of Acetogenins from Annonaceae | journal = Beilstein Journal of Organic Chemistry | year = 2008 | volume = 4 | issue = 48 | pages = 1–62 | pmid = 19190742 | pmc = 2633664 | doi = 10.3762/bjoc.4.48 | url = http://www.beilstein-journals.org/bjoc/content/pdf/1860-5397-4-48.pdf}} Over 400 members of this family of compounds have been isolated from 51 different species of plants.{{cite journal | last1 = Bermejo | first1 = A. | last2 = Figadère | first2 = B. | last3 = Zafra-Polo | first3 = M.-C. | last4 = Barrachina | first4 = I. | last5 = Estornell | first5 = E. | last6 = Cortes | first6 = D. | title = Acetogenins from Annonaceae: Recent Progress in Isolation, Synthesis and Mechanisms of Action | journal = Natural Product Reports | year = 2005 | volume = 22 | issue = 2 | pages = 269–303 | pmid = 15806200 | doi = 10.1039/B500186M }} Erratum: {{ cite journal | title = Back Matter | journal = Natural Product Reports | year = 2005 | volume = 22 | issue = 3 | pages = 426 | doi = 10.1039/B503508M}} Many acetogenins are characterized by neurotoxicity.{{cite book | doi = 10.1007/978-3-319-22692-7_2| pmid = 26659109 | title = Acetogenins from Annonaceae | volume = 101| pages = 113–230| series = Progress in the Chemistry of Organic Natural Products| year = 2016| last1 = Liaw| first1 = Chih-Chuang| last2 = Liou| first2 = Jing-Ru| last3 = Wu| first3 = Tung-Ying| last4 = Chang| first4 = Fang-Rong| last5 = Wu| first5 = Yang-Chang| isbn = 978-3-319-22691-0}}
Examples include:
Structure
File:Mono-THF acetogenin core.png
Structurally, acetogenins are a series of C-35/C-37 compounds usually characterized by a long aliphatic chain bearing a terminal methyl-substituted α,β-unsaturated γ-lactone ring, as well as one to three tetrahydrofuran (THF) rings.{{Cite journal | doi = 10.1021/np980406d| pmid = 10096871| title = Annonaceous Acetogenins: Recent Progress| journal = Journal of Natural Products| volume = 62| issue = 3| pages = 504–40| year = 1999| last1 = Alali| first1 = Feras Q| last2 = Liu| first2 = Xiao-Xi| last3 = McLaughlin| first3 = Jerry L}} These THF rings are located along the hydrocarbon chain, along with a number of oxygenated moieties (hydroxyls, acetoxyls, ketones, epoxides) and/or double bonds.
| class="wikitable"
|+ style="text-align: left;" | Examples of R-groups for selected acetogenins | |||||
| scope="col" | Compound | scope="col" | R1 | scope="col" | R2 | scope="col" | R3 | scope="col" | R4 | scope="col" | R5 |
|---|---|---|---|---|---|
| scope="row" | 4-deoxyannoreticuin
| OH || OH || H || H || H | |||||
| scope="row" | Annonacin
| OH || OH || H || OH || H | |||||
| scope="row" | Annopentocin A
| OH || H || H || OH || H | |||||
| scope="row" | Dispalin
| OAc || OH || H || OH || H | |||||
| scope="row" | Donnaienin C
| OH || OH || H || OAc || OH | |||||
| scope="row" | Goniotetracin
| OH || OH || H || OH || H | |||||
| scope="row" | Muricoreacin
| OH || H || H || OH || H | |||||
| scope="row" | Tonkinin A
| OH || OH || O || H || H | |||||
| scope="row" | Uvaribonone
| OH || OAc || O || H || H |
Research
Acetogenins have been investigated for their biological properties, but are a concern due to neurotoxicity.{{cite journal | journal = Arabian Journal of Chemistry | title = Annona muricata: A comprehensive review on its traditional medicinal uses, phytochemicals, pharmacological activities, mechanisms of action and toxicity | author = Ana V. Coria-Téllez | author2 = Efigenia Montalvo-Gónzalez | author3 = Elhadi M. Yahia | author4 = Eva N. Obledo-Vázquez | volume = 11 | issue = 5 | pages = 662–691 | doi = 10.1016/j.arabjc.2016.01.004| year = 2018 | doi-access = free }}{{cite journal|doi=10.1016/j.toxlet.2011.05.197|title=Annonaceae fruits and parkinsonism risk: Metabolisation study of annonacin, a model neurotoxin; evaluation of human exposure|year=2011|last1=Le Ven|first1=J.|last2=Schmitz-Afonso|first2=I.|last3=Touboul|first3=D.|last4=Buisson|first4=D.|last5=Akagah|first5=B.|last6=Cresteil|first6=T.|last7=Lewin|first7=G.|journal=Toxicology Letters|volume=205|pages=S50–S51}}{{Cite book | editor = Victor R. Preedy |editor2=Ronald Ross Watson |editor3=Vinood B. Patel | title = Nuts and Seeds in Health and Disease Prevention | publisher = Academic Press | date = 2011 | pages = 434–435}}{{Cite journal | title = Determination of Neurotoxic Acetogenins in Pawpaw (Asimina triloba) Fruit by LC-HRMS | author = Robert A. Levine | author2 = Kristy M. Richards | author3 = Kevin Tran | author4 = Rensheng Luo | author5 = Andrew L. Thomas | author6 = Robert E. Smith | name-list-style = amp | journal = J. Agric. Food Chem. | date = 2015 | volume = 63 | issue = 4 | pages = 1053–1056 | doi = 10.1021/jf504500g | pmid=25594104}}{{cite journal | pmid= 22130466 | doi = 10.1016/j.neuro.2011.10.009| year = 2012| last1 = Potts| first1 = L. F.| title = Annonacin in Asimina triloba fruit: Implication for neurotoxicity| journal = Neurotoxicology| volume = 33| issue = 1| pages = 53–8| last2 = Luzzio| first2 = F. A.| last3 = Smith| first3 = S. C.| last4 = Hetman| first4 = M| last5 = Champy| first5 = P| last6 = Litvan| first6 = I}} Purified acetogenins and crude extracts of the common North American pawpaw (Asimina triloba) or the soursop (Annona muricata) remain under laboratory studies.{{cite journal |last1=McLaughlin |first1=J.L. |title=Paw paw and cancer: annonaceous acetogenins from discovery to commercial products. |journal=Journal of Natural Products |year=2008 |volume=71 |issue=7 |pages=1311–21 |pmid=18598079 |doi=10.1021/np800191t}}
Mechanism of action
Acetogenins inhibit NADH dehydrogenase, a key enzyme in energy metabolism.{{cite journal |last1=Eposti|first1=M|date=1 July 1994|title=Natural substances (acetogenins) from the family Annonaceae are powerful inhibitors of mitochondrial NADH dehydrogenase (Complex I).|journal= Biochemical Journal|volume=301|issue=1|pages=161–167|doi=10.1042/bj3010161|pmid=8037664|pmc=1137156}}
References
{{reflist|2}}
External links
- {{commons category-inline}}