- Synthesis of xanthohumol and xanthohumol-d3from naringenin
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A six-step synthesis of xanthohumol (1a) and its d3-derivative (1b) from easily accessible naringenin is reported. The prenyl side chain was introduced by Mitsunobu reaction followed by the europium-catalyzed Claisen rearrangement and base-mediated opening of chromanone gave access to an α,β-conjugated ketone system. Compound1bwas used as an internal standard in stable isotope dilution assays of1ain two Polish beers.
- ?cianowski, Jacek,Andrusiak, Joanna,Budny, Marcin,Mylkie, Kinga,Wolan, Andrzej,Wysocka, Ma?gorzata
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p. 28934 - 28939
(2021/09/22)
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- Microbial conjugation studies of licochalcones and xanthohumol
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Microbial conjugation studies of licochalcones (1–4) and xanthohumol (5) were performed by using the fungi Mucor hiemalis and Absidia coerulea. As a result, one new glucosylated metabolite was produced by M. hiemalis whereas four new and three known sulfated metabolites were obtained by transformation with A. coerulea. Chemical structures of all the metabolites were elucidated on the basis of 1D-, 2D-NMR and mass spectroscopic data analyses. These results could contribute to a better understanding of the metabolic fates of licochalcones and xanthohumol in mammalian systems. Although licochalcone A 4′-sulfate (7) showed less cytotoxic activity against human cancer cell lines compared to its substrate licochalcone A, its activity was fairly retained with the IC50 values in the range of 27.35–43.07 μM.
- Han, Fubo,Xiao, Yina,Lee, Ik-Soo
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- Synthesis and Antiproliferative Activity of Prenylated Chalcone Mannich Base Derivatives
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Prenylated chalcones xanthohumol (1) and 2′-hydroxy-3,4,4′-trimethoxy-6′-O-prenyl chalcone (2) were synthesized through the Claisen–Schmidt condensation, O-prenylation, and Claisen rearrangement and deprotection respectively, using phloroglucinol and appropriate benzaldehydes as starting materials. Based on the Mannich reaction of prenylated chalcone 1 or 2 with various secondary amines and formaldehyde in acid alcohol solvent, 10 novel prenylated chalcone Mannich base derivatives 3a–3e and 4a–4e were synthesized. Furthermore, all synthetic compounds were evaluated for antiproliferative activities in vitro against four human cancer cell lines (Aspc-1, SUN-5, HepG-2, and HCT-116) by MTT assay. The results showed that most of them exhibit moderate to good antiproliferative activities against the four human cancer cells with IC50 values of 2.52 to 47.67 μM.
- Han, Pei-Pei,Liu, Ke-Xiong,Su, Liang,Wang, Qiu-An
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p. 425 - 431
(2021/05/29)
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- Synthesis of xanthohumol analogues and discovery of potent thioredoxin reductase inhibitor as potential anticancer agent
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The selenoprotein thioredoxin reductases (TrxRs) are attractive targets for anticancer drugs development. Xanthohumol (Xn), a naturally occurring polyphenol chalcone from hops, has received increasing attention because of its multiple pharmacological activities. We synthesized Xn and its 43 analogues and discovered that compound 13n displayed the highest cytotoxicity toward HeLa cells (IC50 = 1.4 μM). Structure-activity relationship study indicates that the prenyl group is not necessary for cytotoxicity, and introducing electron-withdrawing group, especially on the meta-position, is favored. In addition, methylation of the phenoxyl groups generally improves the potency. Mechanistic study revealed that 13n selectively inhibits TrxR and induces reactive oxygen species and apoptosis in HeLa cells. Cells overexpressing TrxR are resistant to 13n insult, while knockdown of TrxR sensitizes cells to 13n treatment, highlighting the physiological significance of targeting TrxR by 13n. The clarification of the structural determinants for the potency would guide the design of novel potent molecules for future development.
- Zhang, Baoxin,Duan, Dongzhu,Ge, Chunpo,Yao, Juan,Liu, Yaping,Li, Xinming,Fang, Jianguo
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supporting information
p. 1795 - 1805
(2015/04/27)
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- Xanthohumol, a polyphenol chalcone present in hops, activating nrf2 enzymes to confer protection against oxidative damage in pc12 cells
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Xanthohumol (2a?2,4a?2,4-trihydroxy-6a?2-methoxy-3a?2-prenylchalcone, Xn), a polyphenol chalcone from hops (Humulus lupulus), has received increasing attention due to its multiple pharmacological activities. As an active component in beers, its presence has been suggested to be linked to the epidemiological observation of the beneficial effect of regular beer drinking. In this work, we synthesized Xn with a total yield of 5.0% in seven steps and studied its neuroprotective function against oxidative-stress-induced neuronal cell damage in the neuronlike rat pheochromocytoma cell line PC12. Xn displays moderate free-radical-scavenging capacity in vitro. More importantly, pretreatment of PC12 cells with Xn at submicromolar concentrations significantly upregulates a panel of phase II cytoprotective genes as well as the corresponding gene products, such as glutathione, heme oxygenase, NAD(P)H:quinone oxidoreductase, thioredoxin, and thioredoxin reductase. A mechanistic study indicates that the ?±,?2-unsaturated ketone structure in Xn and activation of the transcription factor Nrf2 are key determinants for the cytoprotection of Xn. Targeting the Nrf2 by Xn discloses a previously unrecognized mechanism underlying the biological action of Xn. Our results demonstrate that Xn is a novel small-molecule activator of Nrf2 in neuronal cells and suggest that Xn might be a potential candidate for the prevention of neurodegenerative disorders.
- Yao, Juan,Zhang, Baoxin,Ge, Chunpo,Peng, Shoujiao,Fang, Jianguo
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p. 1521 - 1531
(2015/03/05)
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- Natural and non-natural prenylated chalcones: Synthesis, cytotoxicity and anti-oxidative activity
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A general strategy for the synthesis of 3′-prenylated chalcones was established and a series of prenylated hydroxychalcones, including the hop (Humulus lupulus L.) secondary metabolites xanthohumol (1), desmethylxanthohumol (2), xanthogalenol (3), and 4-methylxanthohumol (4) were synthesized. The influence of the A-ring hydroxylation pattern on the cytotoxic activity of the prenylated chalcones was investigated in a HeLa cell line and revealed that non-natural prenylated chalcones, like 2′,3,4′,5-tetrahydroxy-6′-methoxy-3′-prenylchalcone (9, IC50 3.2 ± 0.4 μM) as well as the phase 1 metabolite of xanthohumol (1), 3-hydroxyxanthohumol (8, IC50 2.5 ± 0.5 μM), were more active in comparison to 1 (IC50 9.4 ± 1.4 μM). A comparison of the cytotoxic activity of xanthohumol (1) and 3-hydroxyxanthohumol (8) with the non-prenylated analogs helichrysetin (12, IC50 5.2 ± 0.8) and 3-hydroxyhelichrysetin (13, IC50 14.8 ± 2.1) showed that the prenyl side chain at C-3′ has an influence on the cytotoxicity against HeLa cells only for the dihydroxylated derivative. This offers interesting synthetic possibilities for the development of more potent compounds. The ORAC activity of the synthesized compounds was also investigated and revealed the highest activity for compounds 12, 4′-methylxanthohumol (4), and desmethylxanthohumol (2), with 4.4 ± 0.6, 3.8 ± 0.4, and 3.8 ± 0.5 Trolox equivalents, respectively.
- Vogel, Susanne,Ohmayer, Susanne,Brunner, Gabi,Heilmann, Joerg
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p. 4286 - 4293
(2008/12/20)
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- METHOD FOR PRODUCING NARINGENIN DERIVATIVES FROM XANTHOHUMOL
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The invention relates to an efficient method for producing naringenin derivatives from xanthohumol or derivatives thereof. The method comprises, in particular, the production of isoxanthohumol, for example, even in an enantiomer-enriched form, from xanthohumol and subsequently demethylating isoxanthohumol according to specific procedures while obtaining corresponding naringenin derivatives such as 8-prenylnaringenin.
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Page/Page column 11
(2008/06/13)
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- An efficient synthesis of the phytoestrogen 8-prenylnaringenin from xanthohumol by a novel demethylation process
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8-Prenylnaringenin, a flavonoid, is the strongest known phytoestrogen (plant derived estrogen mimic) used in phytomedicinal applications. Starting from xanthohumol a byproduct of hops-extraction, 8-prenylnaringenin can be synthesized via isoxanthohumol. Of various demethylation procedures tested, the best yield (92%) is obtained by treatment with scandium trifluoromethanesulfonate and potassium iodide without any need of protection. The demethylation with AlBr3/collidine and of the TIPS protected isoxanthohumol provides good results too.
- Wilhelm, Heike,Wessjohann, Ludger A.
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p. 6961 - 6966
(2007/10/03)
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- REMEDIES
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According to the present invention, there is provided a medicament for oral administration or intravenous administration that is effective for a disease requiring enhancement of nerve growth factor production, comprising as an effective ingredient a pulverized product and/or extract obtained from Humulus lupulus and/or Angelica keiskei koidz., or xanthohumol and/or a pharmacologically acceptable salt thereof. 'The medicament is useful as a therapeutic agent or prophylactic agent for a disease requiring enhancement of nerve growth factor production, such as dementia or a nerve disorder. Also, according to the present invention, there are provided an enhancing agent for nerve growth factor production, and a food, beverage or feed for enhancing nerve growth factor production, each comprising the above effective ingredient. By taking the food or beverage as foodstuff on a daily basis, the symptoms of a disease requiring enhancement of nerve growth factor production can be ameliorated or the like. In addition, the feed is useful for maintaining homeostasis of a living body by its action of enhancing nerve growth factor production. Furthermore, these medicament and the like of the present invention are effective for improving or ameliorating learning and memorizing ability of an individual organism.
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