8-Prenylnaringenin

8-Prenylnaringenin (8-PN; also known as flavaprenin, (S)-8-dimethylallylnaringenin, hopein, or sophoraflavanone B) is a prenylflavonoid phytoestrogen. It is reported to be the most estrogenic phytoestrogen known.^[1] The compound is equipotent at the two forms of estrogen receptors, ERα and ERβ,^[2] and it acts as a full agonist of ERα.^[3] Its effects are similar to those of estradiol, but it is considerably less potent in comparison.^[2]

8-Prenylnaringenin

Names
IUPAC name (2S)-4′,5,7-Trihydroxy-8-(3-methylbut-2-en-1-yl)flavan-4-one
Systematic IUPAC name (2S)-5,7-Dihydroxy-2-(4-hydroxyphenyl)-8-(3-methylbut-2-en-1-yl)-2,3-dihydro-4H-1-benzopyran-4-one
Other names Hopein; Flavaprenin; Sophoraflavanone B
Identifiers
CAS Number	53846-50-7 Y
3D model (JSmol)	Interactive image
ChEBI	CHEBI:50207 Y
ChemSpider	421848
KEGG	C18023 Y
PubChem CID	480764
UNII	5L872SZR8X Y
CompTox Dashboard (EPA)	DTXSID60333083
InChI InChI=1S/C20H20O5/c1-11(2)3-8-14-15(22)9-16(23)19-17(24)10-18(25-20(14)19)12-4-6-13(21)7-5-12/h3-7,9,18,21-23H,8,10H2,1-2H3/t18-/m0/s1 Key: LPEPZZAVFJPLNZ-SFHVURJKSA-N InChI=1/C20H20O5/c1-11(2)3-8-14-15(22)9-16(23)19-17(24)10-18(25-20(14)19)12-4-6-13(21)7-5-12/h3-7,9,18,21-23H,8,10H2,1-2H3/t18-/m0/s1 Key: LPEPZZAVFJPLNZ-SFHVURJKBX
SMILES CC(=CCC1=C2C(=C(C=C1O)O)C(=O)C[C@H](O2)C3=CC=C(C=C3)O)C
Properties
Chemical formula	C20H20O5
Molar mass	340.375 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

8-PN is found in hops (Humulus lupulus) and in beer, and is responsible for the estrogenic effects of the former.^[2][4] It can be produced from isoxanthohumol in fungal cells cultures,^[5] and by flora in the human intestine.^[1][6]

Properties

Estrogenic

8-PN was shown to preserve bone density^[1] and has been demonstrated to reduce hot flashes.^[1][7] 8-PN also induces the secretion of prolactin, and increases other estrogenic responses.^[8] The compound binds to and activates ERα more times^{[clarification needed]} than it does to ERβ.^[1][2][9]

This prenylflavanoid has drawn interest in the study of hormone replacement therapy, and it is comparable to some selective estrogen-receptor modulators.^[10][11]

In an in vivo study, 8-PN has activated proliferation of mammary cells.^[8] At the concentration found in beer, it is unlikely to have an estrogenic effect in breast tissue.^[12] Similar to other estrogens, 8-PN induces the expression of the progesterone receptor in various tissues.^[8]

Luteinizing hormone (LH) and follicle stimulating hormone (FSH) are suppressed by 8-PN, indicating that it possesses antigonadotropic properties.^[8] 8-PN adversely affects male sperm.^[13] The role 8-PN plays in fertility requires further research.

Other

In an in vitro study, 8-PN and synthetic derivatives demonstrated anticancer properties.^[14] More recently, a radioligand binding study showed enhancements in GABA_A receptor activity by 8-PN^[15]

Prenylflavonoids from hops, including 8-PN, are ingredients in some breast enlargement supplements,^[16] though there is no evidence of its effectiveness for this purpose.^[17]

Chemistry

The enzyme naringenin 8-dimethylallyltransferase uses dimethylallyl diphosphate and (−)-(2S)-naringenin to produce diphosphate and sophoraflavanone B (8-prenylnaringenin).

The enzyme 8-dimethylallylnaringenin 2'-hydroxylase uses sophoraflavanone B (8-prenylnaringenin), NADPH, H⁺ and O₂ to produce leachianone G, NADP⁺ and H₂O.

Synthesized derivatives of 8-PN are: 7,4′-di-O-methyl-8-prenylnaringenin; 7-O-pentyl-8-prenylnaringenin; 7,4′-Di-O-allyl-8-prenylnaringenin; 7,4′-Di-O-acetyl-8-prenylnaringenin; and 7,4′-Di-O-palmitoyl-8-prenylnaringenin.^[14]

8-Neopentylnaringenin and 8-n-heptylnaringenin are synthetic derivatives of 8-PN.^[18]

Etymology

There is another compound, 8-isopentenylnaringenin,^[1] also known as sophoraflavanone B, from Sophora flavescens, that could properly be called 8-prenylnaringenin by scientific naming convention.^[19]