- Neuroregenerative Potential of Prenyl- And Pyranochalcones: A Structure-Activity Study
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Loss of neuronal tissue is a hallmark of age-related neurodegenerative diseases. Since adult neurogenesis has been confirmed in the human brain, great interest has arisen in substances stimulating the endogenous neuronal regeneration mechanism based on ad
- Aigner, Ludwig,Bieler, Lara,Couillard-Despres, Sebastien,Priglinger, Eleni,Riepl, Herbert M.,Urmann, Corinna
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supporting information
p. 2675 - 2682
(2021/10/12)
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- Total Synthesis of the Neuroprotective Agent Cudraisoflavone J
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Cudraisoflavone J (1), isolated fromCudrania tricuspidata, is a potent neuroprotective compound with a chiral center. Herein, we report the first total synthesis of racemic cudraisoflavone J (1) using a Claisen rearrangement and a Suzuki coupling reaction as the key steps. Racemic secondary alcohol was kinetically resolved to give (+)- and (?)-cudraisoflavone J with up to 97 and 88% enantiomeric excess, respectively. The modified Mosher’s method was used to elucidate the absolute configuration of naturally occurring cudraisoflavone J.
- Lu, Qili,Harmalkar, Dipesh S.,Quan, Guofeng,Kwon, Haeun,Cho, Jungsook,Choi, Yongseok,Lee, Dongho,Lee, Kyeong
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p. 1359 - 1365
(2021/05/07)
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- Synthesis of rottlerone analogues and evaluation of their -glucosidase and DPP-4 dual inhibitory and glucose consumption-promoting activity
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Our previous study found that desmethylxanthohumol (1) inhibited α-glucosidase in vitro. Recently, further investigations revealed that dehydrocyclodesmethylxanthohumol (2) and its dimer analogue rottlerone (3) exhibited more potent α-glucosidase inhibito
- Dodd, Robert H.,Lu, Kui,Sun, Hua,Wang, Haibo,Wu, Yan,Yan, Zhihong,Yu, Peng,Zhang, Yinan,Zhao, Xue
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- COMPOUNDS HAVING HEPATIAL DISEASE EFFECTIVE
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The invention discloses a compound with a hepatopathy curative effect, and the compound is a compound shown as a general formula (I), an optical isomer or pharmaceutically acceptable salt thereof, canbe applied to treatment or prevention of hepatopathy, particularly to drugs for treating or preventing fatty liver, liver fibrosis or liver cirrhosis, and has a good application prospect.
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Paragraph 0153-0155
(2021/01/29)
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- An Efficient Regioselective Synthesis of 8-Formylhomoisoflavonoids with Neuroprotective Activity by Enhancing Autophagy
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6-Formylisoophiopogonone B (7a) and 8-formylophiopogonone B (7b), two natural products isolated fromOphiopogonjaponicus, represent a subgroup of rare 6/8-formyl/methyl-homoisoflavonoid skeletons. Herein we report an efficient method for the synthesis of these formyl/methyl-homoisoflavonoids. The synthesized compounds were evaluated for their neuroprotective effects on the MPP+-induced SH-SY5Y cell injury model and showed marked activity. Exploration of the neuroprotective mechanisms of compound7bled to an increased expression of autophagy marker LC3-II and down-regulation of autophagy substrate p62/SQSTM1. Molecular docking studies showed that7bmay prevent the inhibition of the classic PI3K-AKT-mTOR signaling pathway by interfering with the human HSP90AA1.
- Li, Jie,Yang, Fan,Zeng, Lin-Wei,Zhang, Fang-Min,Zhou, Chang-Xin,Gan, Li-She
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p. 1385 - 1391
(2021/04/12)
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- Anti‐melanogenic properties of velutin and its analogs?
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Velutin, one of the flavones contained in natural plants, has various beneficial activities, such as skin whitening, as well as anti‐inflammatory, anti‐allergic, antioxidant, and antimicrobial activities. However, the relationship between the structure of velutin and its anti‐melanogenesis activity is not yet investigated. In this study, we obtained 12 velutin derivatives substituted at C5, C7, C3′, and C4′ of the flavone backbone with hydrogen, hydroxyl, and methoxy functionalities by chemical synthesis, to perform SAR analysis of velutin structural analogues. The SAR study revealed that the substitution of functional groups at C5, C7, C3′, and C4′ of the flavone backbone affects biological activities related to melanin synthesis. The coexistence of hydroxyl and methoxy at the C5 and C7 position is essential for inhibiting tyrosinase activity. However, 1,2‐diol compounds substituted at C3′ and C4′ of flavone backbone induce apoptosis of melanoma cells. Further, substitution at C3′ and C4′ with methoxy or hydrogen is essential for inhibiting melanogenesis. Thus, this study would be helpful for the development of natural‐derived functional materials to regulate melanin synthesis.
- Choe, Jung-Won,Heo, Hee-Young,Jung, Se-Hui,Kim, Jaehyun,Lee, Kooyeon
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- Alkyne-tagged apigenin, a chemical tool to navigate potential targets of flavonoid anti-dengue leads
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A flavonoid is a versatile core structure with various cellular, immunological, and phar-macological effects. Recently, flavones have shown anti-dengue activities by interfering with viral translation and replication. However, the molecular target is still elusive. Here we chemically mod-ified apigenin by adding an alkyne moiety into the B-ring hydroxyl group. The alkyne serves as a chemical tag for the alkyne-azide cycloaddition reaction for subcellular visualization. The compound located at the perinuclear region at 1 and 6 h after infection. Interestingly, the compound signal started shifting to vesicle-like structures at 6 h and accumulated at 24 and 48 h after infection. Moreover, the compound treatment in dengue-infected cells showed that the compound restricted the viral protein inside the vesicles, especially at 48 h. As a result, the dengue envelope proteins spread throughout the cells. The alkyne-tagged apigenin showed a more potent efficacy at the EC50 of 2.36 ± 0.22, and 10.55 ± 3.37 μM, respectively, while the cytotoxicities were similar to the original apigenin at the CC50 of 70.34 ± 11.79, and 82.82 ± 11.68 μM, respectively. Molecular docking con-firmed the apigenin binding to the previously reported target, ribosomal protein S9, at two binding sites. The network analysis, homopharma, and molecular docking revealed that the estrogen receptor 1 and viral NS1 were potential targets at the late infection stage. The interactions could attenuate dengue productivity by interfering with viral translation and suppressing the viral proteins from trafficking to the cell surface.
- Badavath, Vishnu Nayak,Boonyasuppayakorn, Siwaporn,Chokmahasarn, Thamonwan,Hengphasatporn, Kowit,Jansongsaeng, Somruedee,Kaewmalai, Benyapa,Khotavivattana, Tanatorn,Rungrotmongkol, Thanyada,Saelee, Thanaphon,Shigeta, Yasuteru
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- Polymethoxy flavone derivative with anti-hepatitis A virus activity as well as preparation method and application of polymethoxy flavone derivative
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The invention belongs to the field of medicinal chemistry, and relates to a polymethoxy flavone derivative with anti-hepatitis A virus activity as well as a preparation method and application of the polymethoxy flavone derivative. The polymethoxylated fla
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Paragraph 0026-0028
(2021/06/26)
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- Synthesis method of isolicoflavonol
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The invention provides a synthesis method of isolicoflavonol, which comprises the following steps: carrying out condensation reaction on 2,4-O-R1(protective group, the same below)-6-hydroxyacetophenone and 4-O-R2(protective group, the same below)-benzaldehyde to generate 2',4'-O-R1-6'-hydroxy-4-O-R2-chalcone; oxidizing the chalcone to generate flavonol; carrying out selective protection on 3-OH ofthe flavonol to obtain 3,5,7-O-R1-4'-O-R2-flavonol; removing the protecting group R2 from the 3,5,7-O-R1-4'-O-R2-flavonol to obtain 3,5,7-O-R1-4'-hydroxyflavonol; carrying out 1,1-dimethylpropargyl reaction on the 4,4'-OH site to obtain 3,5,7-O-R1-4'-O-(1',1''-dimethyl propargyl)flavonol; carrying out partial hydrogenation on the alkynyl of the 3,5,7-O-R1-4'-O-(1',1''-dimethyl propargyl)flavonolunder the action of a catalyst to obtain 3,5,7-O-R1-4'-O-(1',1''-dimethylpropenyl)flavonol and carrying out Claisen rearrangement on the 3,5,7-O-R1-4'-O-(1',1''-dimethylpropenyl)flavonol to obtain 3,5,7-O-R1-isolicoflavonol, and removing the protecting group R1 from the 3,5,7-O-R1-isolicoflavonol to obtain the isolicoflavonol.
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- Total Synthesis of Sophoraflavanone H and Confirmation of Its Absolute Configuration
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Sophoraflavanone H (1) is a polyphenol with a hybrid-type structure containing 2,3-diaryl-2,3-dihydrobenzofuran and flavanone ring moieties. This compound and related analogues are promising leads for antimicrobial and antitumor drug development. Here we
- Asakawa, Tomohiro,Egi, Masahiro,Hiza, Aiki,Inai, Makoto,Ishikawa, Ryo,Ishikawa, Yoshinobu,Kan, Toshiyuki,Kondo, Mitsuru,Murakami, Haruka,Muramatsu, Yoshihiro,Ouchi, Hitoshi,Taniguchi, Tohru,Tokumaru, Yohei,Tsukaguchi, Yuta,Yoshimura, Fumihiko
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supporting information
(2020/05/25)
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- Synthesis of natural 3′-Prenylchalconaringenin and biological evaluation of ameliorating non-alcoholic fatty liver disease and metabolic syndrome
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Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and important risk factor for cardiac diseases, diabetes and extrahepatic cancers. Natural 3′-geranylchalconaringenin (GC) and desmethylxanthohumol (DX) from hop w
- Zhang, Mengdi,Wang, Zhaoxin,Hao, Siyu,Hao, Lei,Zhang, Xinying,Yu, Peng,Sun, Hua
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- Extensive structure modification on luteolin-cinnamic acid conjugates leading to BACE1 inhibitors with optimal pharmacological properties
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BACE1 inhibitory conjugates derived from two natural products, luteolin (1) and p-hydroxy-cinnamic acid (2), were subjected to systematic structure modifications, including various positions in luteolin segment for conjugation, different linkers (length, bond variation), as well as various substitutions in cinnamic acid segment (various substituents on benzene, and replacement of benzene by heteroaromatics and cycloalkane). Optimal conjugates such as 7c and 7k were chosen on the basis of a series of bioassay data for further investigation.
- Sun, De-Yang,Cheng, Chen,Moschke, Katrin,Huang, Jian,Fang, Wei-Shuo
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supporting information
(2020/01/13)
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- Total synthesis of novel skeleton flavan-alkaloids
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The first total synthesis of novel skeleton natural compounds kinkeloids A and B, a group of newly discovered flavan alkaloids isolated fromthe African plant Combretum micranthum, are described in this study. The key and final step are achieved by Mannich reaction, through which the piperidine moiety couples to the flavan moiety. The identities of synthesized kinkeloids were further confirmed through a comparison with the ones in the plant leaves extract using LC/MS.
- Simon, James E.,Wu, Qingli,Zhen, Jing
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- Rottlerin: Structure Modifications and KCNQ1/KCNE1 Ion Channel Activity
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The slow delayed rectifier potassium current (IKs) is formed by the KCNQ1 (Kv7.1) channel, an ion channel of four α-subunits that modulates KCNE1 β-subunits. IKs is central to the repolarization of the cardiac action potential. Loss of function mutation reducing ventricular cardiac IKs cause the long-QT syndrome (LQTS), a disorder that predisposes patients to arrhythmia and sudden death. Current therapy for LQTS is inadequate. Rottlerin, a natural product of the kamala tree, activates IKs and has the potential to provide a new strategy for rational drug therapy. In this study, we show that simple modifications such as penta-acetylation or penta-methylation of rottlerin blunts activation activity. Total synthesis was used to prepare side-chain-modified derivatives that slowed down KCNQ1/KCNE1 channel deactivation to different degrees. A binding hypothesis of rottlerin is provided that opens the way to improved IKs activators as novel therapeutics for the treatment of LQTS.
- K?rber, Florian,Lübke, Marco,Le Quoc, Thang,Müller, Jasmin,Matschke, Veronika,Scherkenbeck, Jürgen,Schreiber, Julian A.,Schubert, Janina,Seebohm, Guiscard,Sivanathan, Sivatharushan,Strutz-Seebohm, Nathalie
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supporting information
(2020/05/25)
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- Process for preparing flavonoid derivatives and the intermediate thereof
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The present invention provides: a method for manufacturing a flavonoid derivative using a reaction for synthesizing a chalcone derivative by a protection/deprotection reaction of a hydroxyl group and an aldol condensation reaction; and an intermediate thereof. By the method for manufacturing the flavonoid derivative of the present invention can manufacture the flavonoid derivative such as velutin and homoeriodictyol, the present invention can be usefully used in industrial fields such as cosmetics requiring mass production of flavonoid derivatives.
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Paragraph 0112-0115
(2020/10/03)
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- Synthesis and Antifungal Activity of Chromones and Benzoxepines from the Leaves of Ptaeroxylon obliquum
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This study reports the first total synthesis of the bioactive oxepinochromones 12-O-acetyleranthin (8) (angular isomer) and 12-O-acetylptaeroxylinol (9) (linear isomer). The antifungal activity of these compounds and their derivatives was determined against Candida albicans and Cryptococcus neoformans. Most compounds had good selectivity between the two fungi and showed moderate to good activity. 12-O-Acetyleranthin (8) had the highest activity against C. albicans, with an MIC value of 9.9 μM, while 12-O-acetylptaeroxylinol (9), the compound present in Ptaeroxylon obliquum, had the highest activity against C. neoformans, with an MIC value of 4.9 μM.
- Malefo, Modibo S.,Ramadwa, Thanyani E.,Famuyide, Ibukun M.,McGaw, Lyndy J.,Eloff, Jacobus N.,Sonopo, Molahlehi S.,Selepe, Mamoalosi A.
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p. 2508 - 2517
(2020/09/15)
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- Design, synthesis and antiproliferative activity evaluation of fluorine-containing chalcone derivatives
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A series of new chalcones containing fluoro atom at B ring have been designed, synthesized, and evaluated to be antiproliferative activity against a panel of human tumor cell lines. Some of the analogs (8, 9, 12, 45, 46 and 48) displayed powerful antiproliferative effects to certain human tumor cells, but all of them were devoid of any cytotoxicity towards the normal HEK 293. Acridine orange staining data supported that the cytotoxic and antiproliferative effects of the synthesized analogs on tumor cells are mediated through apoptosis. The compounds 12 and 46 manifested concentration-dependent antiproliferative activity in human hepatocellular carcinoma cell lines using an xCELLigence assay. The structures and antiproliferative activity relationship were further supported by in silico molecular docking study of the compounds against tubulin protein which suggests our compounds interference to cell division. Communicated by Ramaswamy H. Sarma.
- Aktas Anil, Derya,Algul, Oztekin,Burmaoglu, Serdar,Duran, Nizami,Gobek, Arzu,Kilic, Deryanur,Yetkin, Derya
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- Synthesis of Flavonols via Pyrrolidine Catalysis: Origins of the Selectivity for Flavonol versus Aurone
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A novel synthetic method for flavonol from 2′-hydroxyl acetophenone and benzaldehyde promoted by pyrrolidine under an aerobic condition in water is established. This protocol was supported by efficient synthesis of 44 common examples and three natural products. The α, β-unsaturated iminium ion (enimine ion E) was proved to be the key intermediate in the reaction. H218O and 18O2 isotope tracking experiments demonstrated that both water and the aerobic atmosphere were necessary to ensure the transformation. The selectivity for flavonol or aurone was originated from solvent-triggered intermediates, which were determined by UV-visible spectra from isolated enimine. The phenol-iminium E-A is dominant in water and the ketoenamine intermediate E-B is prevalent in acetonitrile. In the presence of pyrrolidine and oxygen, E-A leads to flavonol through E-I, a zwitterionic-like phenoloxyl-iminium ion, following the key steps of cyclization and a [2 + 2] oxidation; E-B proceeds through path II, a radical process induced by photolysis of E-B with both pyrrolidine and oxygen, to afford aurone. Preliminary mechanistic studies are reported.
- Xiong, Wei,Wang, Xiaohong,Shen, Xianyan,Hu, Cuifang,Wang, Xin,Wang, Fei,Zhang, Guolin,Wang, Chun
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p. 13160 - 13176
(2020/11/23)
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- New methods to assess 6-thiopurine toxicity and expanding its therapeutic application to pancreatic cancer via small molecule potentiators
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6-Thiopurine (6TP) is a potent cytotoxic agent that is a clinically prescribed anti-metabolite employed in the treatment of numerous blood cancers since 1952. However, its reported severe toxicities limit its general usage in the clinic. We previously have undertaken investigations into identifying the mode of toxicity for 6TP, and have found that the oxidative metabolites of 6TP, specifically 6-thiouric acid (6TU), is responsible for the in vitro inhibition of UDP-glucose dehydrogenase (UDPGDH) in a UV-vis method. In this method, inhibition was quantified through the quantification of NADH production, however, purines absorb at the same wavelength and thereby can interfere with the NADH detection. Herein, we report a HPLC method that allows for direct quantification of UDP-glucuronic acid, product from UDPGDH, for the assessment of inhibition towards UDPGDH with no interference from purines. In this method it was revealed that 6TP possesses a greater inhibitory properties than previously observed; 111 vs. 288 μM. Building upon the data collected from a previously performed rat hepatocyte study, which correlated our in vitro to in vivo inhibition theories about UDPGDH, we have developed a bio-mimic in vitro assay to aid in the inhibitory assessment of 6TP and analogs. In our efforts to expand the use of 6TP, and analogs constructed, our laboratory has undertaken a screening campaign to identify small molecule potentiators that work in synergy with 6TP in other types of cancers. Three chalcone-based compounds have been discovered through our total synthesis campaign of uvaretin, and it has been found that 11c has strong synergism with 6TP in the pancreatic cancer cell line MIA PaCa-2. Through the work presented herein, we reveal new methods to assess toxicity of 6TP and future analogs and new small molecules that work in synergy to expand the therapeutic applications of this neglected cytotoxic agent.
- Weeramange, Chamitha,Lansakara, Ashabha,Dallman, Johnathan,Nguyen, Thi,Hulangamuwa, Wasundara,Rafferty, Ryan J.
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p. 717 - 725
(2019/05/29)
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- The winding road of the uvaretin class of natural products: From total synthesis to bioactive agent discovery
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Herein, we disclose the development of a synthetic route to gain access to the uvaretin class of chalcone natural products. In this, the construction of a small library was achieved, and the collection was evaluated for cytotoxicity and other biological properties. Uvaretin (1) was accessed via a seven-step route in an overall yield of 15.1%. Within this route, the unsaturated enone variant of uvaretin (2), also a natural product, was accessed in a 16.7% yield over six steps. This route provides a nearly three-fold increase in yields of 1 and 2 in comparison to the previous synthetic route accessing them in 5.8% and 3.0% overall yields, respectively. Evaluation of 1 and 2 revealed IC50 values between 2.0 and 5.1 μM in the cancerous cell lines HeLa, U937, A549, and MIA PaCa-2. Screening of the whole chalcone library set led to the discovery of over 30 compounds, within six cancerous cell lines, possessing single digit μM IC50 activity as sole agents. Furthermore, multiple library members were found to possess promising potentiating properties with known chemotherapeutic agents.
- Dallman, Johnathan,Lansakara, Ashabha,Nguyen, Thi,Weeramange, Chamitha,Hulangamuwa, Wasundara,Rafferty, Ryan J.
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p. 1420 - 1431
(2019/08/21)
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- Flavone derivative and preparation method and medical application of flavone derivative
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The invention relates to a flavone derivative and a preparation method and medical application of the flavone derivative. The flavone derivative is prepared through a mode that anhydroicaritin is taken as a mother nucleus, and group addition and reduction are conducted. It is proved through a pharmacological experiment that the flavone derivative has the pharmacological effect of activating endogenous stem cells in the body, achieves the effects of repairing injury-type pathological changes of blood vessel cells, nerve cells, endothelial cells and the matrix and recovering functions, can be used for preparing medicines for repairing the tissue-injury pathological changes and has a good prospect in preparing medicines for conducting rehabilitation treatment on erectile dysfunction pathological changes.
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Paragraph 0084; 0085
(2019/09/05)
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- Preparation and medical application methods of icaritin derivative
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The invention relates to preparation and medical application methods of an icaritin derivative. The preparation method comprises taking trihydroxyacetophenone, chloromethyl methyl ether and the like as initial raw materials to connect isopentene groups to an 8th carbon through vicinal rearrangement, then performing serial reaction of formation of a flavone framework, and lastly, performing dehydration to introduce propylene groups to synthesize the icaritin derivative. The preparation method of the icaritin derivative is low in the cost of the synthetic routes, simple in operation, high in recovery rate and applicable to industrial production. Pharmacological effect experiments prove that the icaritin derivative has the pharmacological effect of activating organism endogenous stem cells and achieves the rehabilitation function of repair traumatic pathological changes of blood vessels, nerves, endothelial cells and matrixes and can be applied to preparing drugs for repairing traumatic pathological changes of tissues, thereby having a good prospect in fields such as drugs for rehabilitation of pathological changes of erectile dysfunction.
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Paragraph 0067; 0068; 0069; 0080; 0081; 0082; 0094
(2019/10/23)
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- A kind of A ring with methyl of [...] compound, preparation method and anti-inflammatory activity
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The invention discloses a quinoid chalcone compound with a methyl group at an A ring, and a preparation method and anti-inflammatory activity thereof. The compound has a structure as shown in a general formula (I) which is described in the specification. The preparation method comprises the following steps: (1) synthesizing 2-hydroxy-4,6-dimethoxyacetophenone; (2) synthesizing 2'-hydroxy-4',6'-dimethoxychalcone derivative; (3) synthesizing 2',4',6'-trihydroxy chalcone derivative; and (4) synthesizing the quinoid chalcone compound with a methyl group at the A ring. The compound is simple to prepare and has obvious anti-inflammatory action.
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Paragraph 0059; 0060; 0061; 0062; 0063; 0064; 0073-0076
(2019/04/18)
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- Compound for treating or preventing hepatopathy (by machine translation)
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The invention discloses a compound, an optical isomer or a pharmaceutically acceptable salt, an optical isomer or a pharmaceutically acceptable salt thereof for treating or preventing hepatopathy, and the compound, optical isomer or pharmaceutically acceptable salt thereof can be applied to the preparation of a medicine for treating or preventing liver diseases. (by machine translation)
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Paragraph 0135-0136; 0138
(2019/10/01)
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- Drug compound for treating hepatopathy and application thereof
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The invention discloses a drug compound for treating hepatopathy and application thereof. The drug compound specifically serves as a compound shown in general formula (I) or an optical isomer or a pharmaceutically-acceptable salt of the compound. The compound or the optical isomer or the pharmaceutically-acceptable salt of the compound has a good curative effect and low toxicity on hepatopathy, especially fatty liver. Experiments show that the compound has an obvious protective effect on zebrafish nonalcoholic fatty liver, so that the drug compound has a good application prospect in medicinesfor treatment or prevention of hepatopathy, especially fatty liver or liver fibrosis or liver cirrhosis.
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Paragraph 0148-0149; 0151
(2019/10/15)
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- Synthesis, biological evaluation, and molecular docking of dihydroflavonol derivatives as anti-inflammatory agents
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A series of dihydroflavonol derivatives (4a–4l) were synthesized from chalcones via classical Algar–Flynn–Oyamada (AFO) reaction and characterized on the basis of spectroscopic analyses. All synthesized compounds were evaluated for their inhibitory activity against the pro-inflammatory-inducible TNF-alpha, IL-1beta, and IL-6 in lipopolysaccharide (LPS)-stimulated RAW 264.7 cell lines and showed various efficiency. Furthermore, compounds 4d and 4k were selected to examine their in vivo anti-inflammatory activity by using two classical models. Herein compound 4k showed maximum anti-inflammatory activity of 32.98% inhibition in mice ear-swelling model and 40.06% inhibition at the 2 h intervals in rat paw edema model in comparison to the two references: aspirin and meloxicam. Similar effect was observed at a lower dose. In addition, the compound 4k was docked against cyclooxygenases-2 to validate the attained pharmacological data and provide understandable evidence for the observed anti-inflammatory activity.
- Xiang, Yuanhang,Hu, Chunling,Zhang, Yuejie,Ye, Xiaochuan
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p. 863 - 872
(2019/04/17)
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- Cytosine N-isoflavone compound as well as preparation method and application thereof
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The invention relates to a cytosine N-isoflavone compound as well as a preparation method and application thereof. The compound has a structural formula as shown in the specification, wherein R1 is selected from one of hydroxyl, alkoxy, amido or halo, R2 is selected from one of hydrogen, alkyl or aryl, and R3 is selected from one or a combination of several of hydroxyl, alkoxy, amido or halo. Compared with the prior art, the cytosine N-isoflavone compound has the characteristic that an isoflavone compound serving as a structural unit is spliced to N on the 12th position of cytosine by using acombined synthesis technology, so that a series of cytosine-isoflavone derivatives are synthesized, and a novel active pharmacological action is exerted.
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Paragraph 0029-0036
(2019/10/02)
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- Synthesis method and uses of natural product Xanthohumol D and analogue thereof
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The invention discloses a synthesis method and uses of a natural product Xanthohumol D (I) and an analogue (II) thereof, wherein the structural formula is defined the specification, the novel isopentenyl chalcone compound is obtained, and Xanthohumol D has good inhibitory activity on bacillus subtilis. According to the invention, the preparation method has advantages of few process steps and easily available raw materials, and is suitable for industrial production.
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Paragraph 0006; 0036
(2019/12/31)
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- Fluorine-substituted flavanonol compound as well as preparation method and application thereof
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The invention discloses a fluorine-substituted flavanonol compound. The compound has the following structure (shown in the description), wherein any one of R1, R2, R3, R4 and R5 in a general formula is one of F, CF3, SF5, SCF2 or SCF3, and the balance of
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Paragraph 0027-0029
(2018/04/01)
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- Total synthesis of viscumneoside III of Viscum coloratum
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The first total synthesis of viscumneoside III, a promising anti-angina pectoris dihydroflavone O-glycoside isolated from Viscum coloratum was described here. Trichloroaceti-midate was employed as the apiofuranosyl donor to construct the key building block of homoeriodictyol-7-O-β-D-apiosyl-(1 → 2)-β-D-glycoside (1). The longest linear sequence (from 2 to 1) in the synthetic route required thirteen steps and afforded the final product 1 with an overall yield of 6.3%.
- Zou, Lei,Zhang, Zixue,Chen, Xiaowen,Chen, Hua,Zhang, Yi,Li, Jianqi,Liu, Yu
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p. 2376 - 2382
(2018/04/06)
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- Flavanonol compound containing N aromatic heterocycte and preparation method and application thereof
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The invention discloses a flavanonol compound containing N aromatic heterocycte, which has a following structure in a specification, wherein an Ar substituent in a formula I is shown as one in the specification, and the substituted position of the compoun
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Paragraph 0024; 0025; 0026; 0046; 0047; 0048
(2018/04/02)
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- Discovery of flavonoids from scutellaria baicalensis with inhibitory activity against PCSK 9 expression: Isolation, synthesis and their biological evaluation
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Nine flavonoids were isolated and identified from a chloroform-soluble fraction of the roots of Scutellaria baicalensis through a bioactivity-guided fractionation using a proprotein convertase subtilisin/kexin type 9 (PCSK9) monitoring assay in HepG2 cell
- Nhoek, Piseth,Chae, Hee-Sung,Masagalli, Jagadeesh Nagarajappa,Mailar, Karabasappa,Pel, Pisey,Kim, Young-Mi,Choi, Won Jun,Chin, Young-Won
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- 5′-Chloro-2,2′-dihydroxychalcone and related flavanoids as treatments for prostate cancer
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Several flavonoids and their biosynthetic precursor chalcones were designed and synthesized to improve the biological effects of the lead compound 2′-hydroxyflavonone against androgen receptor (AR)-dependent transcriptional stimulation. Newly synthesized chalcones 19 and 26 suppressed AR-dependent transcription as well as DHT-dependent growth stimulation at a low micromolar level. These compounds were also effective against ligand-independent constitutively active mutant AR derived from castration-resistant PCa (CRPC). Compounds 19 and 26 showed broad spectrum antiproliferative activity at 5–10 μM against multiple tumor cell lines including androgen-independent and taxane-resistant prostate cancer as well as a multidrug-resistant subline. Mode of action studies suggested that 19 induced sub-G1 accumulation in PC-3 cells by disrupting the microtubule network without affecting cell cycle progression. Furthermore, the in vivo effectiveness of chalcone 19 was confirmed in a xenograft model antitumor assay. Thus, chalcone 19 has the potential to be a bifunctional lead for treatment of AR-dependent PCa at lower doses as well as AR-independent PCa, including CRPC, at higher doses.
- Saito, Yohei,Mizokami, Atsushi,Tsurimoto, Hiroyuki,Izumi, Kouji,Goto, Masuo,Nakagawa-Goto, Kyoko
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supporting information
p. 1143 - 1152
(2018/09/10)
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- Synthesis and antiangiogenic activity study of new hop chalcone Xanthohumol analogues
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Angiogenesis induction is a hallmark of cancer. Antiangiogenic properties of Xanthohumol (XN), a naturally occurring prenylated chalcone from hops, have been widely reported. Here we describe the synthesis and study the antiangiogenic activity in vitro of
- Nuti, Elisa,Bassani, Barbara,Camodeca, Caterina,Rosalia, Lea,Cantelmo, AnnaRita,Gallo, Cristina,Baci, Denisa,Bruno, Antonino,Orlandini, Elisabetta,Nencetti, Susanna,Noonan, Douglas M.,Albini, Adriana,Rossello, Armando
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p. 890 - 899
(2017/07/26)
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- Synthesis and biological evaluation of novel flavanone derivatives as potential antipsychotic agents
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In this study, a series of novel flavanone derivatives were designed and synthesized, and the antipsychotic activities of the target compounds were evaluated in vitro and in vivo. The results showed that synthesized compounds 7a–7g decreased the activity of dopamine D2 receptors in HEK293 cells co-transfected with D2 receptor/G protein α16a, with IC50 values of 0.051–0.35?μm. Compounds 7a–7g inhibited the over-production of nitric oxide stimulated by lipopolysaccharide/interferon-γ in BV-2 microglial cells. In mice, intragastric administration of 7d, 7e, and 7g reversed the increase in locomotor activity induced by MK-801 (an antagonist of NMDA receptors) and decreased the hyperactivity of climbing behavior induced by apomorphine (a dopamine receptor agonist). These results suggest that some of the novel flavanone derivatives have potential antipsychotic effects and may be useful in the treatment of schizophrenia.
- Gu, Hong-Shun,Chen, Xi,Zhang, Jian-Wei,Zhang, Lan,Li, Lin
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p. 353 - 364
(2017/04/03)
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- Synthesis and antioxidant evaluation of desmethylxanthohumol analogs and their dimers
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Four ring-closed analogs of natural prenylated chalcone desmethylxanthohumol (1) and their dimers were synthesized from the commercially available 1-(2,4,6-trihydroxyphenyl)ethan-1-one in five and six linear steps, respectively. The structures of the eigh
- Teng, Yuou,Li, Xuzhe,Yang, Ke,Li, Xuehui,Zhang, Zijun,Wang, Luyao,Deng, Zhijie,Song, Binbin,Yan, Zhihong,Zhang, Yongmin,Lu, Kui,Yu, Peng
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p. 335 - 345
(2016/10/03)
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- Total synthesis and metabolic stability of hispidulin and its d-labelled derivative
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Hispidulin is a naturally occurring flavone known to have various Central nervous system (CNS) activities. Proposed synthetic approaches to synthesizing hispidulin have proven unsatisfactory due to their low feasibility and poor overall yields. To solve these problems, this study developed a novel scheme for synthesizing hispidulin, which had an improved overall yield as well as more concise reaction steps compared to previous methods reported. Additionally, using the same synthetic strategy, d-labelled hispidulin was synthesized to investigate its metabolic stability against human liver microsome. This work may produce new chemical entities for enriching the library of hispidulin-derived compounds.
- Chen, Liang-Chieh,Hsu, Kai-Cheng,Chiou, Lih-Chu,Tseng, Hui-Ju,Huang, Wei-Jan
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- Design of potent fluoro-substituted chalcones as antimicrobial agents
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Owing to ever-increasing bacterial and fungal drug resistance, we attempted to develop novel antitubercular and antimicrobial agents. For this purpose, we developed some new fluorine-substituted chalcone analogs (3, 4, 9–15, and 20–23) using a structure–a
- Burmaoglu, Serdar,Algul, Oztekin,Gobek, Arzu,Aktas Anil, Derya,Ulger, Mahmut,Erturk, Busra Gul,Kaplan, Engin,Dogen, Aylin,Aslan, G?nül
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p. 490 - 495
(2017/11/10)
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- Efficient synthesis of rottlerin and its two subunits
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Rottlerin, a natural product isolated from Mallotus philippensis, is associated with a range of biological activities. Its chemical structure is featured by two different substituted phloroglucinol units linked by a methylene group. In this study, we accomplished a total synthesis of rottlerin using phenol-aldehyde condensation as the key reaction. By our method, gram-scale preparation of the two structural subunits was achieved, and rottlerin was obtained in a longest eight linear step with 20% overall yield. Our study provides a practical solution for obtaining the sample of rottlerin in an efficient way.
- Li, Yangfeng,Yu, Biao,Wang, Renxiao
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supporting information
p. 1856 - 1859
(2016/04/19)
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- Synthesis and biological evaluation of 5,7-dihydroxyflavanone derivatives as antimicrobial agents
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A series of 5,7-dihydroxyflavanone derivatives were efficiently synthesized. Their antimicrobial efficacy on Gram-negative, Gram-positive bacteria and yeast were evaluated. Among these compounds, most of the halogenated derivatives exhibited the best antimicrobial activity against Gram-positive bacteria, the yeast Saccharomyces cerevisiae, and the Gram-negative bacterium Vibrio cholerae. The cytotoxicities of these compounds were low as evaluated on HepG2 cells using a cell viability assay. This study suggests that halogenated flavanones might represent promising pharmacological candidates for further drug development.
- Zhang, Xing,Khalidi, Omar,Kim, So Young,Wang, Ruitong,Schultz, Victor,Cress, Brady F.,Gross, Richard A.,Koffas, Mattheos A.G.,Linhardt, Robert J.
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supporting information
p. 3089 - 3092
(2016/06/13)
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- Total Synthesis and in Vitro Anti-Tumor-Promoting Activities of Racemic Acetophenone Monomers from Acronychia trifoliolata
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Six acetophenone derivatives, acronyculatins I (1), J (2), K (3), L (4), N (5), and O (6), were recently isolated from Acronychia trifoliolata, and the structure of the known acronyculatin B (7) was revised. Because of the limited quantities of isolated p
- Morita, Chihiro,Kobayashi, Yukiko,Saito, Yohei,Miyake, Katsunori,Tokuda, Harukuni,Suzuki, Nobutaka,Ichiishi, Eiichiro,Lee, Kuo-Hsiung,Nakagawa-Goto, Kyoko
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supporting information
p. 2890 - 2897
(2016/12/07)
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- Synthesis and anti-proliferative activity of fluoro-substituted chalcones
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A series of novel fluoro-substituted chalcone derivatives have been synthesized. All synthesized compounds were characterized by 1H nuclear magnetic resonance (NMR), 13C NMR, and elemental analysis. Their anti-proliferative activities were evaluated against five cancer cells lines, namely, A549, A498, HeLa, A375, and HepG2 using the MTT method. Most of the compounds showed moderate to high activity with IC50 values in the range of 0.029-0.729 μM. Of all the synthesized compounds, 10 and 19 exhibited the most potent anti-proliferative activities against cancer cells, and 10 was identified as the most promising compound.
- Burmaoglu, Serdar,Algul, Oztekin,Anil, Derya Aktas,Gobek, Arzu,Duran, Gulay Gulbol,Ersan, Ronak Haj,Duran, Nizami
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p. 3172 - 3176
(2016/06/13)
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- Eriodictyol synthesis method
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The invention provides an eriodictyol synthesis method. According to the eriodictyol synthesis method, isovanillin and 2,4,6-trihydroxyacetophenone are selected as starting materials, and eriodictyol is obtained through the following five steps: firstly, performing MOMCl protection on a hydroxyl of isovanillin; secondly, performing MOMCl protection on a hydroxyl of 2,4,6-trihydroxyacetophenone; thirdly, performing an aldol condensation reaction to generate chalcone; fourthly, performing Michael addition and cyclization; finally, carrying out MOM deprotection to obtain eriodictyol of which the total yield is 50-65%. As isovanillin and 2,4,6-trihydroxyacetophenone are selected as the starting materials, the eriodictyol synthesis method is high in yield and suitable for industrialized production.
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Paragraph 0024; 0027
(2016/10/07)
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- BENZOTHIOPHENE DERIVATIVE HAVING ANTI-CANCER EFFECT
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PROBLEM TO BE SOLVED: To provide a novel compound that has an excellent anti-cancer effect. SOLUTION: Provided is a benzothiophene derivative represented by formula (1), or a pharmaceutically acceptable salt thereof. [R1 is H, OH, a halogeno group, a C1 to 12 alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, an alkylamino group or an alkylthio group, a substituted/unsubstituted aryl group, a substituted/unsubstituted benzyl group, or a substituted/unsubstituted carbon ring or heterocyclic ring condensed to 5-6 position; R2 is H, OH, a halogeno group, a C1 to 12 alkyl group, an alkenyl group, an alkynyl group, an alkoxy group, an alkylamino group or an alkylthio group; a substituted/unsubstituted aryl group or a substituted/unsubstituted benzyl group.] SELECTED DRAWING: Figure 1 COPYRIGHT: (C)2016,JPO&INPIT
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Paragraph 0012
(2018/09/25)
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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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- 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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p. 1795 - 1805
(2015/04/27)
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- A Biomimetic Strategy to Access the Silybins: Total Synthesis of (-)-Isosilybin A
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(Figure Presented). We report the first asymmetric, total synthesis of (-)-isosilybin A. A late-stage catalytic biomimetic cyclization of a highly functionalized chalcone is employed to form the characteristic benzopyranone ring. A robust and flexible app
- McDonald, Benjamin R.,Nibbs, Antoinette E.,Scheidt, Karl A.
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supporting information
p. 98 - 101
(2015/07/28)
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- The first total synthesis of sophoflavescenol, flavenochromane C, and citrusinol
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The first total syntheses of sophoflavescenol (1), flavenochromane C (2), and citrusinol (3) were achieved. These three naturally occurring prenylated or prenyl-cyclized flavonoids have important biological activities such as cytotoxicity against some can
- Nguyen, Van-Son,Dong, Lin-Pei,Wang, Sheng-Chun,Wang, Qiuan
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p. 2297 - 2302
(2015/04/14)
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- Synthesis, structure-activity relationship studies, and antibacterial evaluation of 4-chromanones and chalcones, as well as olympicin A and derivatives
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On the basis of recently reported abyssinone II and olympicin A, a series of chemically modified flavonoid phytochemicals were synthesized and evaluated against Mycobacterium tuberculosis and a panel of Gram-positive and -negative bacterial pathogens. Some of the synthesized compounds exhibited good antibacterial activities against Gram-positive pathogens including methicillin resistant Staphylococcus aureus with minimum inhibitory concentration as low as 0.39 μg/mL. SAR analysis revealed that the 2-hydrophobic substituent and the 4-hydrogen bond donor/acceptor of the 4-chromanone scaffold together with the hydroxy groups at 5- and 7-positions enhanced antibacterial activities; the 2′,4′-dihydroxylated A ring and the lipophilic substituted B ring of chalcone derivatives were pharmacophoric elements for antibacterial activities. Mode of action studies performed on selected compounds revealed that they dissipated the bacterial membrane potential, resulting in the inhibition of macromolecular biosynthesis; further studies showed that selected compounds inhibited DNA topoisomerase IV, suggesting complex mechanisms of actions for compounds in this series.
- Feng, Li,Maddox, Marcus M.,Alam, Md. Zahidul,Tsutsumi, Lissa S.,Narula, Gagandeep,Bruhn, David F.,Wu, Xiaoqian,Sandhaus, Shayna,Lee, Robin B.,Simmons, Charles J.,Tse-Dinh, Yuk-Ching,Hurdle, Julian G.,Lee, Richard E.,Sun, Dianqing
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p. 8398 - 8420
(2015/02/19)
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- Total syntheses of Nigrasin i and Kuwanon C
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The efficient total syntheses of Nigrasin I and Kuwanon C, two biologically interesting natural flavonoids with two regioisomeric isoprenyl side chains, were realized for the first time starting from commercially available 1-(2,4,6-trihydroxyphenyl)ethano
- Tang, Fei,Wang, Yang,Hou, Ai-Jun
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p. 3963 - 3970
(2014/06/09)
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