53846-50-7

Usage

Uses

Used in Pharmaceutical Industry:
8-PRENYLNARINGENIN is used as a pharmaceutical agent for its potential estrogenic effects. It can be employed in the development of treatments for conditions related to hormonal imbalances, such as menopause symptoms, osteoporosis, and certain types of cancer.
Used in Nutraceutical Industry:
8-PRENYLNARINGENIN is used as a nutraceutical ingredient for its potential health benefits. It can be incorporated into dietary supplements and functional foods to support hormonal balance and promote overall well-being.
Used in Cosmetic Industry:
8-PRENYLNARINGENIN is used as an active ingredient in cosmetic products for its potential skin health benefits. It can be formulated into creams, lotions, and serums to help improve skin elasticity, reduce wrinkles, and maintain a youthful appearance.
Used in Agricultural Industry:
8-PRENYLNARINGENIN can be used as a natural plant growth regulator in the agricultural industry. It may help improve crop yield, enhance resistance to diseases, and promote overall plant health.

Biological Activity

8-prenylnaringenin is an estrogen receptor inhibitor.the two estrogen receptors erα and erβ belong to the nuclear receptor superfamily and are ligand-regulated transcription factors accounting for mediating the physiological effects of the steroid hormone 17α-estradiol. er is an established target for the development of synthetic ligands for therapeutic applications.

in vitro

previous study identified 8-prenylnaringenin as a potent phytoestrogen in hops, which had an activity greater than other known plant estrogens. the estrogenic activity of 8-prenylnaringenin was reflected in its relative binding affinity to estrogen receptors from rat uteri. in addition, the presence of 8-prenylnaringenin in hops might explane the accounts of menstrual disturbances in female hop workers [1].

in vivo

previous animal data demonstrated that 8-prenylnaringenin treatment could result in ampk signaling pathway activation, therefore suppressing lipogenesis. the consumption of 8-prenylnaringenin was able to prevent body weight gain and improve plasma lipid profile, with significant improvement of insulin resistance and glucose tolerance. moreove, it was found that 8-prenylnaringenin-enriched diet could ameliorate diabetic-associated metabolic disturbances via regulating glucose and lipid pathways [2].

IC 50

57 and 68 nm for erα and erβ, respectively

references

[1] milligan sr, kalita jc, heyerick a, rong h, de cooman l, de keukeleire d. identification of a potent phytoestrogen in hops (humulus lupulus l.) and beer. j clin endocrinol metab. 1999 jun;84(6):2249-52.[2] costa r et al. xanthohumol and 8-prenylnaringenin ameliorate diabetic-related metabolic dysfunctions in mice. j nutr biochem. 2017 apr 6;45:39-47.

Upstream product

• 115-18-4 2-methyl-3-buten-2-ol 
• 480-41-1 naringenin 
• 68682-02-0 5,7-Dihydroxy-2-(4-hydroxy-phenyl)-8-(3-methyl-but-2-enyl)-chroman-4-one 
• 780724-90-5 dimethylallyl diphosphate 
• 1141487-32-2 2-(4-acetoxyphenyl)-8-(3-methylbut-2-enyl)-4-oxochroman-5,7-diyl diacetate 
• 3682-04-0 (S)-2-(4-acetoxyphenyl)-4-oxochromane-5,7-diyl diacetate 
• 358-72-5 dimethylallyl diphosphate 
• 334701-04-1 2-(4-acetoxyphenyl)-5-hydroxy-8-(3-methylbut-2-enyloxy)-4-oxochroman-7-yl acetate 
• 70872-29-6 Isoxanthohumol 
• 569-83-5 xanthohumol 

Downstream Products

• 152464-78-3 8-dimethylallylsteppogenin 

Relevant academic research and scientific papers

Prenylflavonoids: A new class of non-steroidal phytoestrogen (Part 1). Isolation of 8-isopentenylnaringenin and an initial study on its structure- activity relationship

Bioassay-guided fractionation of a methanolic extract of a Thai crude drug, derived from heartwood of Anaxagorea luzonensis A. Gray (Annonaceae), resulted in the isolation of 8-isopentenylnaringenin (1) as an estrogen agonist with an activity of about an order of magnitude greater than genistein. Various flavonoids possessing isopentenyl side chains in the A- ring have been prepared and evaluated for their ability to bind estrogen receptor. In addition, enantiomers of 1 were separated and the respective enantiomers were assayed. These studies have demonstrated that the presence of an 8-isopentenyl group is an important factor for binding. Flavones, flavanones and flavonols having an isopentenyl substituent at C-8 exhibited an appreciable affinity for estrogen receptor. Conversely, isoflavones possessing an 8-isopentenyl substituent at C-8 did not show this activity. Movement of the isopentenyl group from position 8 to 6 resulted in loss of the activity. No significant difference was observed between 2(S)- and 2(R)- enantiomers of 1 in their binding affinity. Prenylflavonoids are reported to possess a wide range of biological activities; however, estrogenic activity has not been described.

In vitro effect of 8-prenylnaringenin and naringenin on fibroblasts and glioblastoma cells-cellular accumulation and cytotoxicity

Gliomas are one of the most aggressive and treatment-resistant types of human brain cancer. Identification and evaluation of anticancer properties of compounds found in plants, such as naringenin (N) and 8-prenylnaringenin (8PN), are among the most promising applications in glioma therapy. The prenyl group seems to be crucial to the anticancer activity of flavones, since it may lead to enhanced cell membrane targeting and thus increased intracellular activity. It should be noted that 8PN content in hop cones is 10 to 100 times lower compared to other flavonoids, such as xanthohumol. In the study presented, we used a simple method for the synthesis of 8PN from isoxanthohumol - O-demethylation, with a high yield of 97%. Cellular accumulation and cytotoxicity of naringenin and 8-prenylnaringenin in normal (BJ) and cancer cells (U-118 MG) was also examined. Obtained data indicated that 8-prenylnaringenin exhibited higher cytotoxicity against used cell lines than naringenin, and the effect of both flavones was stronger in U-118 MG cells than in normal fibroblasts. The anticancer properties of 8PN correlated with its significantly greater (37%) accumulation in glioblastoma cells than in normal fibroblasts. Additionally, naringenin demonstrated higher selectivity for glioblastoma cells, as it was over six times more toxic for cancer than normal cells. Our results provide evidence that examined prenylated and non-prenylated flavanones have different biological activities against normal and cancer cell lines, and this property may be useful in designing new anticancer drugs for glioblastoma therapy.

Formation of (2 R)- And (2 S)-8-Prenylnaringenin Glucuronides by Human UDP-Glucuronosyltransferases

Occurring in hops (Humulus lupulus) and beer as a racemic mixture, (2R,2S)-8-prenylnaringenin (8-PN) is a potent phytoestrogen in hop dietary supplements used by women as alternatives to conventional hormone therapy. With a half-life exceeding 20 h, 8-PN is excreted primarily as 8-PN-7-O-glucuronide or 8-PN-4′-O-glucuronide. Human liver microsomes and 11 recombinant human UDP-glucuronosyltransferases (UGTs) were used to catalyze the formation of the two oxygen-linked glucuronides of purified (2R)-8-PN and (2S)-8-PN, which were subsequently identified using mass spectrometry and nuclear magnetic resonance spectroscopy. Formation of (2R)- and (2S)-8-PN-7-O-glucuronides predominated over the 8-PN-4′-O-glucuronides except for intestinal UGT1A10, which formed more (2S)-8-PN-4′-O-glucuronide. (2R)-8-PN was a better substrate for all 11 UGTs except for UGT1A1, which formed more of both (2S)-8-PN glucuronides than (2R)-8-PN glucuronides. Although several UGTs conjugated both enantiomers of 8-PN, some conjugated just one enantiomer, suggesting that human phenotypic variation might affect the routes of metabolism of this chiral estrogenic constituent of hops.

Semi-Synthetic Approach Leading to 8-Prenylnaringenin and 6-Prenylnaringenin: Optimization of the Microwave-Assisted Demethylation of Xanthohumol Using Design of Experiments

The isomers 8-prenylnaringenin and 6-prenylnaringenin, both secondary metabolites occurring in hops, show interesting biological effects, like estrogen-like, cytotoxic, or neuro regenerative activities. Accordingly, abundant sources for this special flavonoids are needed. Extraction is not recommended due to the very low amounts present in plants and different synthesis approaches are characterized by modest yields, multiple steps, the use of expensive chemicals, or an elaborate synthesis. An easy synthesis strategy is the demethylation of xanthohumol, which is available due to hop extraction industry, using lithium chloride and dimethylformamide, but byproducts and low yield did not make this feasible until now. In this study, the demethylation of xanthohumol to 8-prenylnaringenin and 6-prenylnaringenin is described the first time and this reaction was optimized using Design of Experiment and microwave irradiation. With the optimized conditions—temperature 198 ?C, 55 eq. lithium chloride, and a reaction time of 9 min, a final yield of 76% of both prenylated flavonoids is reached.

Regio- and stereospecific prenylation of flavonoids by Sophora flavescens prenyltransferase

Prenylflavonoids are valuable natural products that are widely distributed in plants. They often possess divergent biological properties, including phytoestrogenic, anti-bacterial, anti-tumor, and anti-diabetic activities. The reaction catalyzed by prenyltransferases represents a Friedel-Crafts alkylation of the flavonoid skeleton in the biosynthesis of natural prenylflavonoids and often contributes to the structural diversity and biological activity of these compounds. However, only a few plant flavonoid prenyltransferases have been identified thus far, and these prenyltransferases exhibit strict substrate specificity and low catalytic efficiency. In this article, a flavonoid prenyltransferase from Sophora flavescens, SfFPT, has been identified that displays high catalytic efficiency with high regiospecificity acting on C-8 of structurally different types of flavonoid (i.e., flavanone, flavone, flavanonol, and dihydrochalcone, etc.). Furthermore, SfPFT exhibits strict stereospecificity for levorotatory flavanones to produce (2S)-prenylflavanones. This study is the first to demonstrate the substrate promiscuity and stereospecificity of a plant flavonoid prenyltransferase in vitro. Given its substrate promiscuity and high catalytic efficiency, SfFPT can be used as an environmentally friendly and efficient biological catalyst for the regio- and stereospecific prenylation of flavonoids to produce bioactive compounds for potential therapeutic applications. Copyright

A practical access to highly enantiomerically pure flavanones by catalytic asymmetric transfer hydrogenation

A surprisingly selective, non-enzymatic kinetic resolution of readily available, racemic β-chiral ketones enabled the title process, which was applied to a rapid synthesis of several bioactive flavanones in virtually enantiopure form (see scheme; MOM=methoxymethyl, Ts=p-toluenesulfonyl). Copyright

An efficient method for C8-prenylation of flavonols and flavanones

Synthesis of C8-prenylated flavonols and flavanones via the palladium-catalyzed 7-O-1,1-dimethylprop-2-enylation, followed by Claisen rearrangement is described. Two regioselectivities (carbon-carbon bond formation at either the tail or head of the prenyl

Flavanone 8-dimethylallyltransferase in Sophora flavescens cell suspension cultures

Dimethylallyl diphosphate: naringenin 8-dimethylallyltransferase (EC 2.5.1) was characterized. The enzyme was enantiospecific for (-)-(2S)-naringenin and utilized 3,3-dimethylallyl diphosphate as sole prenyl donor. It required Mg2+ (optimum concentration, 10 mM), and has an optimum pH of 9-10. The apparent K(m) values for 3,3-dimethylallyl diphosphate and naringenin were 120 and 36 μM, respectively. The microsomal fraction prenylated several other flavanones at the C-8 position less effectively as compared with naringenin. Interestingly, when 2'-hydroxynaringenin was used as a prenyl acceptor, the 8-lavandulyl (sophoraflavanone G) and the 6-dimethylallyl derivatives were formed, together with the 8-dimethylallyl derivative, leachianone G. These results suggest that the 2'-hydroxy group of naringenin plays an important role for the formation of a lavandulyl group. (C) 2000 Elsevier Science Ltd.

PRENYLATED FLAVONOIDS IN THE ROOTS OF YELLOW LUPIN

A further investigation of the methanol-soluble compounds in yellow lupin roots has revealed a new diprenylchromone, a new coumaronochromone (lupinalbin H), a new isoflavone 5,7,4'-trihydroxy-8,3'-di-(3,3-dimethylallyl)isoflavone (isolupalbigenin), and so