Flavones

{{Short description|Class of flavonoid chemical compounds}} thumb|Molecular structure of the flavone backbone with numbers

'''Flavones''' (from Latin ''flavus'' "yellow") are a class of flavonoids based on the backbone of 2-phenylchromen-4-one (2-phenyl-1-benzopyran-4-one) (as shown in the first image of this article).<ref name="lpi-flav">{{cite web|url=http://lpi.oregonstate.edu/mic/dietary-factors/phytochemicals/flavonoids|title=Flavonoids|publisher=Micronutrient Information Center, Linus Pauling Institute, Oregon State University, Corvallis, OR|date=November 2015|access-date=30 March 2018}}</ref><ref>{{cite web|url=http://www.chemspider.com/Chemical-Structure.10230.html|title=Flavone|publisher=ChemSpider, Royal Society of Chemistry|date=2015|access-date=30 March 2018}}</ref>

Flavones are common in foods, mainly from spices, and some yellow or orange fruits and vegetables.<ref name=lpi-flav/> Common flavones include apigenin (4',5,7-trihydroxyflavone), luteolin (3',4',5,7-tetrahydroxyflavone), tangeritin (4',5,6,7,8-pentamethoxyflavone), chrysin (5,7-dihydroxyflavone), and 6-hydroxyflavone.<ref name=lpi-flav/>

==Intake and elimination== The estimated daily intake of flavones is about 2&nbsp;mg per day.<ref name=lpi-flav/> Following ingestion and metabolism, flavones, other polyphenols, and their metabolites are absorbed poorly in body organs and are rapidly excreted in the urine, indicating mechanisms influencing their presumed absence of metabolic roles in the body.<ref name=lpi-flav/><ref name="LPI">{{cite web|url=http://www.eurekalert.org/pub_releases/2007-03/osu-sfn030507.php|title=Studies force new view on biology of flavonoids|author=David Stauth|publisher=EurekAlert!; Adapted from a news release issued by Oregon State University|date=5 March 2007|access-date=28 November 2014|archive-date=4 December 2019|archive-url=https://web.archive.org/web/20191204110942/https://www.eurekalert.org/pub_releases/2007-03/osu-sfn030507.php|url-status=dead}}</ref>

==Drug interactions== Flavones have effects on CYP (P450) activity,<ref>{{cite journal |vauthors=Cermak R, Wolffram S |title=The potential of flavonoids to influence drug metabolism and pharmacokinetics by local gastrointestinal mechanisms |journal=Curr Drug Metab |date=Oct 2006 |volume=7 |issue=7 |pages=729–744|doi=10.2174/138920006778520570 |pmid=17073577 }}</ref><ref>{{cite journal |vauthors=Si D, Wang Y, Zhou YH |title=Mechanism of CYP2C9 inhibition by flavones and flavonols |journal=Drug Metab. Dispos. |volume=37 |issue=3 |pages=629–34 |date=March 2009 |pmid=19074529 |doi=10.1124/dmd.108.023416 |s2cid=285706 |display-authors=etal}}[http://p4502c.googlepages.com/dmd2.pdf] {{Webarchive|url=https://web.archive.org/web/20081217093507/http://p4502c.googlepages.com/dmd2.pdf |date=2008-12-17 }}</ref> which are enzymes that metabolize most drugs in the body.

==Biosynthesis== thumb|upright=2|Synthesis of apigenin to depict general flavone biosynthesis. The biosynthesis of flavones proceeds from the phenylpropanoid pathway, which uses L-phenylalanine as a starting point.<ref name="Ferrer Austin 2008">{{cite journal |vauthors=Ferrer JL, Austin MB |date=2008 |title=Structure and function of enzymes involved in the biosynthesis of phenylpropanoids |journal=Plant Physiol. Biochem |volume=46 |issue=3 |pages=356–370 |doi=10.1016/j.plaphy.2007.12.009|pmid=18272377 |pmc=2860624 |bibcode=2008PlPB...46..356F }}</ref> Phenylalanine ammonia lyase facilitates the deamination of L-phenylalanine to (E)-cinnamate,<ref name="Ferrer Austin 2008"/> which is then oxidized by cinnamate 4-hydroxylase to yield p-Coumaric acid.<ref>{{cite journal |vauthors=Mizutani M, Ohta D, Sato R |title=Isolation of a cDNA and a genomic clone encoding cinnamate 4-hydroxylase from Arabidopsis and its expression manner in plants |journal=Plant Physiology |volume=113 |pages=755–763 |date=1997 |issue=3 |doi=10.1104/pp.113.3.755|pmid=9085571 |pmc=158193 |s2cid=10059931 }}</ref> Coenzyme A is attached to the carboxylate facilitated by 4-Coumarate-CoA ligase, forming (Coumaroyl-CoA).<ref name="Ferrer Austin 2008"/> A chalcone synthase then facilitates a series of condensation reactions in the presence of 3 malonyl CoA ending with a ring-forming Claisen condensation yielding a chalcone (naringenin chalcone is shown),<ref>{{cite journal |vauthors=Ferrer JL, Jez JM |date=1999 |title=Structure of chalcone synthase and the molecular basis of plant polyketide biosynthesis |journal=Nat. Struct. Biol. |volume=6 |issue=8 |pages=775–784 |doi=10.1038/11553|pmid=10426957 |s2cid=23408591 }}</ref> which is subsequently isomerized by chalcone isomerase resulting in a flavanone (naringenin is shown).<ref>{{cite journal |vauthors=Jez JM, Bowman ME |date=2000 |title=Structure and mechanism of the evolutionarily unique plany enzyme chalcone isomerase |journal=Nat. Struct. Biol. |volume=7 |issue=9 |pages=786–791 |doi=10.1038/79025|pmid=10966651 |s2cid=22198011 }}</ref> It is at this point that the flavanone can undergo further modifications (such as glycosylation or methylation at the various points of the backbone. The subsequent modified flavanones are then transformed into flavones by flavone synthase, which generates a double bond between the C-2 and C-3 positions (the synthesis of apigenin is shown).<ref>{{cite journal |vauthors=Martens S, Mithofer A |date=2005 |title=Flavones and flavone synthases |journal=Phytochemistry |volume=66 |issue=20 |pages=2399–2407 |doi=10.1016/j.phytochem.2005.07.013|pmid=16137727 |bibcode=2005PChem..66.2399M }}</ref>

==Organic chemistry== In organic chemistry several methods exist for the synthesis of flavones:<ref name="pmid37764304">{{cite journal |vauthors=Leonte D, Ungureanu D, Zaharia V |title=Flavones and Related Compounds: Synthesis and Biological Activity |journal=Molecules |volume=28 |issue=18 |date=2023 |page=6528 |pmid=37764304 |pmc=10535985 |doi=10.3390/molecules28186528 |doi-access=free |url=}}</ref> *Allan–Robinson reaction *Auwers synthesis *Baker–Venkataraman rearrangement *Algar–Flynn–Oyamada reaction

Another method is the dehydrative cyclization of certain 1,3-diaryl diketones.<ref>{{cite journal |vauthors=Sarda SR, Pathan MY, Paike VV, Pachmase PR, Jadhav WN, Pawar RP |title=A facile synthesis of flavones using recyclable ionic liquid under microwave irradiation |journal=Arkivoc |volume=xvi |issue=16 |pages=43–8 |year=2006 |doi=10.3998/ark.5550190.0007.g05 |doi-access=free |hdl=2027/spo.5550190.0007.g05 |hdl-access=free }}</ref>

400px|Flavone synthesis from 1,3-ketones

==={{anchor|Wessely-Moser rearrangement}} Wessely–Moser rearrangement===

The '''Wessely–Moser rearrangement''' (1930)<ref>{{cite journal |vauthors=Wessely F, Moser GH |title=Synthese und Konstitution des Skutellareins |journal=Monatshefte für Chemie |volume=56 |issue=1 |pages=97–105 |date=December 1930 |doi=10.1007/BF02716040 |s2cid=95833443 }}</ref> has been an important tool in structure elucidation of flavonoids. It involves the conversion of 5,7,8-trimethoxyflavone into 5,6,7-trihydroxyflavone on hydrolysis of the methoxy groups to phenol groups. It also has synthetic potential for example:<ref>{{cite journal |vauthors=Larget R, Lockhart B, Renard P, Largeron M |title=A convenient extension of the Wessely-Moser rearrangement for the synthesis of substituted alkylaminoflavones as neuroprotective agents in vitro |journal=Bioorg. Med. Chem. Lett. |volume=10 |issue=8 |pages=835–8 |date=April 2000 |pmid=10782697 |doi=10.1016/S0960-894X(00)00110-4|url=https://hal.archives-ouvertes.fr/hal-02385135/file/Accepted%20Bioorg.%20Med.%20Chem.%202000.pdf }}</ref>

400px|Wessely–Moser rearrangement

This rearrangement reaction takes place in several steps: '''A''' ring opening to the diketone, '''B''' bond rotation with formation of a favorable acetylacetone-like phenyl-ketone interaction and '''C''' hydrolysis of two methoxy groups and ring closure.

== Common flavones == {| class="wikitable sortable" style="text-align:center" |+Flavones and their structure <ref>{{Cite book|title=The Flavonoids - Springer|doi=10.1007/978-1-4899-2909-9|year = 1975|isbn = 978-0-12-324602-8|last1 = Harborne|first1 = Jeffrey B.|last2=Marby|first2=Helga|last3=Marby|first3=T. J.|s2cid=33487001 }}</ref> !Name !Structure !R³ !R⁵ !R⁶ !R⁷ !R⁸ !R^2' !R^3' !R^4' !R^5' !R^6' |- |Flavone backbone | rowspan="60" |200x200px |– |– |– |– |– |– |– |– |– |– |- |Primuletin |– |–OH |– |– |– |– |– |– |– |– |- |Chrysin |– |–OH |– |–OH |– |– |– |– |– |– |- |Tectochrysin |– |–OH |– |–OCH₃ |– |– |– |– |– |– |- |Primetin |– |–OH |– |– |–OH |– |– |– |– |– |- |Apigenin |– |–OH |– |–OH |– |– |– |–OH |– |– |- |Acacetin |– |–OH |– |–OH |– |– |– |–OCH₃ |– |– |- |Genkwanin |– |–OH |– |–OCH₃ |– |– |– |–OH |– |– |- |Echioidinin |– |–OH |– |–OCH₃ |– |–OH |– |– |– |– |- |Baicalein |– |–OH |–OH |–OH |– |– |– |– |– |– |- |Oroxylin A |– |–OH |–OCH₃ |–OH |– |– |– |– |– |– |- |Negletein |– |–OH |–OH |–OCH₃ |– |– |– |– |– |– |- |Norwogonin |– |–OH |– |–OH |–OH |– |– |– |– |– |- |Wogonin |– |–OH |– |–OH |–OCH₃ |– |– |– |– |– |- |Liquiritigenin<ref name="Dewick">{{cite book |last1=Dewick |first1=Paul M. |title=Medicinal Natural Products. A Biosynthetic Approach |date=2009 |publisher=John Wiley & Sons |location=Chichester, UK |isbn=978-0-470-74276-1 |pages=137–186 |chapter=The Shikimate Pathway: Aromatic Amino Acids and Phenylpropanoids | doi = 10.1002/9780470742761.ch4}}</ref> |– |– |– |–OH |– |– |– |–OH |– |– |- |Naringenin<ref name="Dewick"/> |– |–OH |– |–OH |– |– |– |–OH |– |– |- |Geraldone |– |– |– |–OH |– |– |–OCH₃ |–OH |– |– |- |Tithonine |– |– |– |–OCH₃ |– |– |–OH |–OCH₃ |– |– |- |Luteolin |– |–OH |– |–OH |– |– |–OH |–OH |– |– |- |6-Hydroxyluteolin |– |–OH |–OH |–OH |– |– |–OH |–OH |– |– |- |Chrysoeriol |– |–OH |– |–OH |– |– |–OCH₃ |–OH |– |– |- |Diosmetin |– |–OH |– |–OH |– |– |–OH |–OCH₃ |– |– |- |Pilloin |– |–OH |– |–OCH₃ |– |– |–OH |–OCH₃ |– |– |- |Velutin |– |–OH |– |–OCH₃ |– |– |–OCH₃ |–OH |– |– |- |Norartocarpetin |– |–OH |– |–OH |– |–OH |– |–OH |– |– |- |Artocarpetin |– |–OH |– |–OCH₃ |– |–OH |– |–OH |– |– |- |Scutellarein |– |–OH |–OH |–OH |– |– |– |–OH |– |– |- |Hispidulin |– |–OH |–OCH₃ |–OH |– |– |– |–OH |– |– |- |Sorbifolin |– |–OH |–OH |–OCH₃ |– |– |– |–OH |– |– |- |Pectolinarigenin |– |–OH |–OCH₃ |–OH |– |– |– |–OCH₃ |– |– |- |Cirsimaritin |– |–OH |–OCH₃ |–OCH₃ |– |– |– |–OH |– |– |- |Mikanin |– |–OH |–OCH₃ |–OCH₃ |– |– |– |–OCH₃ |– |– |- |Isoscutellarein |– |–OH |– |–OH |–OH |– |– |–OH |– |– |- |Zapotinin |– |–OH |–OCH₃ |– |– |–OCH₃ |– |– |– |–OCH₃ |- |Zapotin |– |–OCH₃ |–OCH₃ |– |– |–OCH₃ |– |– |– |–OCH₃ |- |Cerrosillin |– |–OCH₃ |–OCH₃ |– |– |– |–OCH₃ |– |–OCH₃ |– |- |Alnetin |– |–OH |–OCH₃ |–OCH₃ |–OCH₃ |– |– |– |– |– |- |Tricetin |– |–OH |– |–OH |– |– |–OH |–OH |–OH |– |- |Tricin |– |–OH |– |–OH |– |– |–OCH₃ |–OH |–OCH₃ |– |- |Corymbosin |– |–OH |– |–OCH₃ |– |– |–OCH₃ |–OCH₃ |–OCH₃ |– |- |Nepetin |– |–OH |–OCH₃ |–OH |– |– |–OH |–OH |– |– |- |Pedalitin |– |–OH |–OH |–OCH₃ |– |– |–OH |–OH |– |– |- |Nodifloretin |– |–OH |–OH |–OH |– |– |–OCH₃ |–OH |– |– |- |Jaceosidin |– |–OH |–OCH₃ |–OH |– |– |–OCH₃ |–OH |– |– |- |Cirsiliol |– |–OH |–OCH₃ |–OCH₃ |– |– |–OH |–OH |– |– |- |Eupatilin |– |–OH |–OCH₃ |–OH |– |– |–OCH₃ |–OCH₃ |– |– |- |Cirsilineol |– |–OH |–OCH₃ |–OCH₃ |– |– |–OCH₃ |–OH |– |– |- |Eupatorin |– |–OH |–OCH₃ |–OCH₃ |– |– |– |–OCH₃ |–OH |– |- |Sinensetin |– |–OCH₃ |–OCH₃ |–OCH₃ |– |– |– |–OCH₃ |–OCH₃ |– |- |Hypolaetin |– |–OH |– |–OH |–OH |– |–OH |–OH |– |– |- |Onopordin |– |–OH |– |–OH |–OCH₃ |– |–OH |–OH |– |– |- |Wightin |– |–OH |– |–OCH₃ |–OCH₃ |–OCH₃ |–OH |– |– |– |- |Nevadensin |– |–OH |–OCH₃ |–OH |–OCH₃ |– |– |–OCH₃ |– |– |- |Xanthomicrol |– |–OH |–OCH₃ |–OCH₃ |–OCH₃ |– |– |–OH |– |– |- |Tangeretin |– |–OCH₃ |–OCH₃ |–OCH₃ |–OCH₃ |– |– |–OCH₃ |– |– |- |Serpyllin |– |–OH |– |–OCH₃ |–OCH₃ |–OCH₃ |–OCH₃ |–OCH₃ |– |– |- |Sudachitin |– |–OH |–OCH₃ |–OH |–OCH₃ |– |–OCH₃ |–OH |– |– |- |Acerosin |– |–OH |–OCH₃ |–OH |–OCH₃ |– |–OH |–OCH₃ |– |– |- |Hymenoxin |– |–OH |–OCH₃ |–OH |–OCH₃ |– |–OCH₃ |–OCH₃ |– |– |- |Gardenin D |– |–OH |–OCH₃ |–OCH₃ |–OCH₃ |– |–OH |–OCH₃ |– |– |- |Nobiletin |– |– |–OCH₃ |–OCH₃ |–OCH₃ |–OCH₃ |– |–OCH₃ |–OCH₃ |– |– |- |Scaposin |– |– |–OH |–OCH₃ |–OH |–OCH₃ |– |–OCH₃ |–OCH₃ |–OH |- |- !Name !Structure !R³ !R⁵ !R⁶ !R⁷ !R⁸ !R^2' !R^3' !R^4' !R^5' !R^6' |}

==Research== In one preliminary 2021 study, flavone intake was associated with lower odds of subjective cognitive decline after adjustment for age, total energy intake, major nondietary factors, and specific dietary factors.<ref>{{Cite journal|last1=Yeh|first1=Tian-Shin|last2=Yuan|first2=Changzheng|last3=Ascherio|first3=Alberto|last4=Rosner|first4=Bernard A.|last5=Willett|first5=Walter C.|last6=Blacker|first6=Deborah|date=2021-09-07|title=Long-term Dietary Flavonoid Intake and Subjective Cognitive Decline in US Men and Women|journal=Neurology|language=en|volume=97|issue=10|pages=e1041–e1056|doi=10.1212/WNL.0000000000012454 | pmc=8448553 |issn=0028-3878|pmid=34321362|doi-access=free}}</ref>

==References== {{Reflist}}

==External links== * {{MeshName|Flavones}}

{{Flavonoids}} {{Flavones}}

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Category:Flavones Category:CYP2C9 inhibitors