- Synthesis of montbretin A analogues yields potent competitive inhibitors of human pancreatic α-amylase
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Simplified analogues of the potent human amylase inhibitor montbretin A were synthesised and shown to bind tightly, KI = 60 and 70 nM, with improved specificity over medically relevant glycosidases, making them promising candidates for controlling blood glucose. Crystallographic analysis confirmed similar binding modes and identified new active site interactions.
- Tysoe, Christina R.,Caner, Sami,Calvert, Matthew B.,Win-Mason, Anna,Brayer, Gary D.,Withers, Stephen G.
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Read Online
- Synthesis, characterization and antioxidant activity of quercetin derivatives
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A series of quercetin derivatives were synthesized via Williamson etherification, Steglich esterification or Koenigs–Knorr glycosylation reaction at 3 and 7 position hydroxyl groups selectively. The structures of the synthesized compounds were characteriz
- Sun, Lei,Lu, Bo,Liu, Yandan,Wang, Qian,Li, Gao,Zhao, Longxuan,Zhao, Chunhui
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p. 2944 - 2953
(2021/08/25)
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- Preparation of quercetin combined hydrogen sulfide donor and application of quercetin combined hydrogen sulfide donor in treatment of diabetes and wound healing of diabetes
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The invention belongs to the technical field of preparation of medicines for treating diabetes and healing wounds of the diabetes, and particularly relates to quercetin-3-O-acetic acid-(4-(3H-1,2-dithiole-3-thioketone))-phenyl ester and an application thereof in preparation of medicines for treating diabetes and healing wounds of the diabetes. The preparation comprises the steps: by taking rutin as a raw material, carrying out substitution hydrolysis reaction twice, reducing to generate quercetin-3-O-acetic acid, and carrying out condensation reaction on quercetin-3-O-acetic acid and a hydrogen sulfide donor 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thioketone to successfully prepare a compound entity capable of simultaneously treating diabetes and promoting wound healing. In an HUVECs cell experiment, a cell proliferation experiment verifies that the HUVECs can be promoted to grow, and a scratch experiment and an in-vitro tubule formation experiment further verify that the HUVECs can be promoted to heal wounds of diabetic patients. HepG 2 cytotoxicity experiments prove that the medicine has no damage to liver cells, and through treatment of an insulin resistance model, it is verified that the compound has a similar hypoglycemic effect with a commercially available medicine metformin.
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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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- Regiospecific synthesis of three quercetin O-β-glucosides of N-acetylglucosamine
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The regiospecific synthesis of three quercetin O-β-glucosides of N-acetylglucosamine has been achieved in good yield. Selective di- and tri-O-benzylation of quercetin followed by O-glycosylation with 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-d-glucopyranosyl chloride under phase-transfer catalysis conditions yielded, after deacetylation and debenzylation, 3-, 3′- and 4′-glycosylated quercetin.
- Cao, Zhiling,Chen, Jing,Zhu, Dandan,Yang, Zongnan,Teng, Wenqi,Liu, Gaofeng,Liu, Bing,Tao, Chuanzhou
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p. 189 - 193
(2018/05/26)
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- The first synthesis of 3-O-methylcyanidin and the effect of 3-O-substitution on stability under acidic conditions
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The simplest and most common anthocyanin in nature is 3-O-glucosylcyanidin (1), and 3-O-glucosylation is believed to stabilize the chromophore. To clarify the effect of the glucose residue we compared the stability of 1 with its aglycone, cyanidin (2), an
- El-Meligy, Asmaa B.,Ishihara, Takehiro,Oyama, Kin-Ichi,El-Nahas, Ahmed M.,Yoshida, Kumi
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p. 946 - 959
(2019/04/26)
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- Quercetin derivative and preparation method and applications thereof
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The invention discloses a quercetin derivative and a preparation method and applications thereof. The chemical structural formula of the quercetin derivative is represented by the formula (I). The chemical name of the quercetin derivative is 2-(3,4-dihydroxylphenyl)-3-(5-N,N-diethylaminepentyloxy)-5,7-dihydroxyl-4H-1-benzopyran-4-one. The 2-(3,4-dihydroxylphenyl)-3-(5-N,N-diethylaminepentyloxy)-5,7-dihydroxyl-4H-1-benzopyran-4-one is obtained by subjecting quercetin to chemical modification, can inhibit the activity of acetylcholin esterase, and can be used to prepare functional food or drugs for preventing Alzheimer's disease.
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Paragraph 0050; 0051
(2017/12/27)
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- Natural and Synthetic Flavonoids as Potent Mycobacterium tuberculosis UGM Inhibitors
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This study reports a novel class of inhibitors of uridine 5′-diphosphate (UDP) galactopyranose mutase (UGM) derived from a screening of natural products. This enzyme is an essential biocatalyst involved in the cell wall biosynthesis of Mycobacterium tuberculosis. Flavonoids are potent inhibitors of UGM. The synthesis of novel methylated flavonoids allowed a structure–activity relationship analysis to be performed and which functional groups and structural elements were required for UGM inhibition could be determined. The binding mode of one of the best inhibitors was found to be noncompetitive. Docking simulations indicated that this molecule was likely to bind UGM in its open conformation, in a cavity recently identified as a “druggable” pocket. Importantly, two of the best inhibitors of the M. tuberculosis UGM displayed moderate activity against whole M. tuberculosis cells. This study reports the first natural products that act as inhibitor of UGM. Given the importance of natural products in medicinal chemistry, these results create new opportunities for the discovery of new antitubercular agents.
- Villaume, Sydney A.,Fu, Jian,N'Go, Inès,Liang, Hui,Lou, Huayong,Kremer, Laurent,Pan, Weidong,Vincent, Stéphane P.
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p. 10423 - 10429
(2017/08/07)
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- Synthesis of quercetin-3-O-acetate and application of quercetin-3-O-acetate to tumor resistance
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Quercetin has the pharmacological activities of eliminating phlegm, relieving cough, relieving asthma, lowering blood pressure, resisting cancer, resisting viruses, resisting bacteria, resisting oxidation and the like. The structure of quercetin is modified and transformed by utilizing a chemical method, so as to hopefully improve the bioavailability of quercetin and strengthen the pharmacological activities of quercetin. Quercetin selectively protected by benzyl bromide is utilized, and a Williamson reaction is utilized to introduce acetate to the third site of quercetin, so as to synthesize a series of quercetin-3-O-acetate derivants. An MTT method proves that compared with quercetin, the compound can obviously inhibit growth of esophagus cancer cells, and is a novel anti-tumor candidate compound with great potential.
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Paragraph 0025; 0026
(2016/11/17)
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- Synthesis of quercetin glycosides and their α-glucosidase inhibitory activities
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A series of quercetin glycosides as the analogues of 3,5,5'- Trimethyl-7-O-β-D-glucopyranosylquercetin (8) were synthesized, their structures were confirmed by 1H NMR, 13C NMR and MS. The inhibitory activities of those compounds against α-glucosidase were evaluated in vitro, in particular, the compounds V-c and V-d-2 showed promising bioactivities with IC50 of 19.4 μmol·L-1 and 19.7 μmol·L-1, are much higher than 8 (IC50 > 100 μmol·L-1). This research will provide a reference in the study of the synthetic methods and hypoglycemic activity for the quercetin glycosides.
- Xu, Bixue,Liang, Guangyi,Wen, Zhonghang,Hu, Zhanxin,Yuan, Jie,Chen, Hongju,Zhang, Limei
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p. 1245 - 1260
(2016/07/26)
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- Flavone glycoside derivatives, and preparation method and application thereof
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The invention discloses flavone glycoside derivatives which are compounds with a general structural formula I shown in the description, and pharmaceutically acceptable salts or hydrates thereof, including racemates, optical isomers and epimers of the deri
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- Effects of Functional Groups and Sugar Composition of Quercetin Derivatives on Their Radical Scavenging Properties
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Quercetin derivatives are widespread in the plant kingdom and exhibit various biological actions. The aim of this study was to investigate the structure-activity relationships of quercetin derivatives, with a focus on the influence of functional groups and sugar composition on their antioxidant capacity. A series of quercetin derivatives were therefore prepared and assessed for their DPPH radical scavenging properties. Isoquercetin O-gallates were more potent radical scavengers than quercetin. The systematic analysis highlights the importance of the distribution of hydroxy substituents in isoquercetin O-gallates to their potency.
- Kato, Komei,Ninomiya, Masayuki,Tanaka, Kaori,Koketsu, Mamoru
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p. 1808 - 1814
(2016/08/02)
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- Discovery of metal ions chelator quercetin derivatives with potent anti-HCV activities
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Analogues or isosteres of α,γ-diketoacid (DKA) 1a show potent inhibition of hepatitis C virus (HCV) NS5B polymerase through chelation of the two magnesium ions at the active site. The anti-HCV activity of the flavonoid quercetin ( 2) could partly be attri
- Zhong, Dongwei,Liu, Mingming,Cao, Yang,Zhu, Yelin,Bian, Shihui,Zhou, Jiayi,Wu, Fengjie,Ryu, Kum-Chol,Zhou, Lu,Ye, Deyong
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p. 6978 - 6999
(2015/05/13)
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- NOVEL APPROACH FOR SYNTHESIS OF CATECHINS
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A process for synthesis of enatiomerically pure or enatiomerically enriched or racemic mixture of (+and/or?) epicatechin echm and its intermediates, comprising the steps of: (i) obtaining penta-protected quercetin; (ii) reducing the penta-protected quercetin obtained from step (i); (iii) optionally deprotecting the compound of step (ii); (iv) reducing the compound obtained from step (ii) or step (iii) in the presence of a chiral/achiral reducing agent to obtain a chiral intermediate; (v) deprotecting and/or hydrogenation of the chiral intermediate obtained from step (iv) to obtain (?)-epicatechin; (vi) optionally simultaneously deprotecting and by drogenation of the compound obtained from step (ii) to obtain racemic epicatechin.
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Paragraph 0094; 0095
(2016/01/15)
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- Biological evaluation and SAR analysis of O-methylated analogs of quercetin as inhibitors of cancer cell proliferation
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Preclinical Research Using a high-throughout screening approach, the anticancer activities of 16 O-methylated (OMe) analogs of quercetin were assessed. The structure-activity relationships showed that OMe moieties at the 4′ and/or 7 positions were important for maintaining inhibitory activities against the 16 cancer cell lines. Furthermore, when the OH groups at the 3′ and 4′ positions were both replaced by OMe moieties, anticancer activity was enhanced.
- Shi, Zhi-Hao,Li, Nian-Guang,Tang, Yu-Ping,Shi, Qian-Ping,Tang, Hao,Li, Wei,Zhang, Xu,Fu, Hai-An,Duan, Jin-Ao
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p. 455 - 462
(2015/04/14)
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- Flavone-based analogues inspired by the natural product simocyclinone D8 as DNA gyrase inhibitors
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The increasing occurrence of drug-resistant bacterial infections in the clinic has created a need for new antibacterial agents. Natural products have historically been a rich source of both antibiotics and lead compounds for new antibacterial agents. The natural product simocyclinone D8 (SD8) has been reported to inhibit DNA gyrase, a validated antibacterial drug target, by a unique catalytic inhibition mechanism of action. In this work, we have prepared simplified flavone-based analogues inspired by the complex natural product and evaluated their inhibitory activity and mechanism of action. While two of these compounds do inhibit DNA gyrase, they do so by a different mechanism of action than SD8, namely DNA intercalation.
- Verghese, Jenson,Nguyen, Thuy,Oppegard, Lisa M.,Seivert, Lauren M.,Hiasa, Hiroshi,Ellis, Keith C.
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supporting information
p. 5874 - 5877
(2013/10/22)
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- Metabolism-based synthesis, biologic evaluation and SARs analysis of O-methylated analogs of quercetin as thrombin inhibitors
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In blood, quercetin is mainly found in metabolized forms. In order to study the activities of these quercetin metabolites in cardiovascular disease, 17 methylquercetin derivatives were synthesized based on metabolism in vivo, their thrombin inhibition activity were evaluated through the analyzation of prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT) and fibrinogen (FIB). The results showed that 6 methylquercetin derivatives had stronger inhibitory activities than that of quercetin. Preliminary SARs analysis showed that hydroxyl groups at C-3′ and C-4′ position in the B-ring and hydroxyl group at C-3 position in the C-ring played key roles in the thrombin inhibitory activity. The findings of this study would provide information for the exploitation and utilization of quercetin as thrombin inhibitor for thrombotic disease treatment.
- Shi, Zhi-Hao,Li, Nian-Guang,Tang, Yu-Ping,Wei-Li,Lian-Yin,Yang, Jian-Ping,Hao-Tang,Duan, Jin-Ao
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experimental part
p. 210 - 222
(2012/09/07)
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- Synthesis of quercetin 3-O-β-d-apiofuranosyl-(1→2)-[α-l- rhamnopyranosyl-(1→6)]-β-d-glucopyranoside
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A concise method to construct a unique 2,6-branched trisaccharide was established by regioselective glycosylation of three free hydroxyl groups on a 3-O-protected glucose moiety, and successfully used in the synthesis of quercetin 3-O-β-d-apiofuranosyl-(1→2)-[α-l-rhamnopyranosyl- (1→6)]-β-d-glucopyranoside, a flavonol O-glycoside isolated from glandless cotton seeds which showed notable antidepressant activities.
- Zhang, Yang,Wang, Kejun,Zhan, Zhilai,Yang, Yu,Zhao, Yimin
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p. 3154 - 3157
(2011/06/28)
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- Discovering novel quercetin-3-O-amino acid-esters as a new class of Src tyrosine kinase inhibitors
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Quercetin-3-O-amino acid-esters, a new type of quercetin derivatives, were successfully prepared for the first time. Different from quercetin, the novel compounds show higher selectivity as inhibitors against Src tyrosine kinase (IC50 values ra
- Huang, He,Jia, Qi,Ma, Jingui,Qin, Guangrong,Chen, Yingyi,Xi, Yonghua,Lin, Liping,Zhu, Weiliang,Ding, Jian,Jiang, Hualiang,Liu, Hong
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experimental part
p. 1982 - 1988
(2009/09/30)
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- Synthesis of 3-aminoflavones from 3-hydroxyflavones via 3-tosyloxy- or 3-mesyloxyflavones
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Reaction of 3-tosyloxy- or 3-mesyloxyflavones with ammonia or primary amines proceeded to give the corresponding 3-aminoflavones in high yields. 3-Aminoluteorin was efficiently prepared from rutin using this method. Copyright
- Takechi, Atsushi,Takikawa, Hirosato,Miyake, Hideyoshi,Sasaki, Mitsuru
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p. 128 - 129
(2007/10/03)
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