117-39-5Relevant articles and documents
Studies on the medicinal resources. XXXVI. The constituents of the leaves of Saxifraga stolonifera Meerburg (Saxifragaceae)
Morita,Shimizu,Arisawa,Koshi
, p. 1487 - 1489 (1974)
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A triterpene glycoside and flavonoids from leaves of Akebia quinata
Sutiashvili,Alaniya,Skhirtladze,Kemertelidze
, p. 402 - 402 (2008)
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Chemical constituents of apocynum lancifolium flowers
Begmatov,Yili,Eshbakova,Aisa
, (2014)
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Flavonoids from Gleditsia triacanthos
Duchenko,Demeshko,Kovalev
, p. 1093 - 1094 (2016)
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FLAVONOID GLYCOSIDES AND AN ANTHRAQUINONE FROM RUMEX CHALEPENSIS
Hasan, Aurangzeb,Ahmed, Iftikar,Jay, Maurice,Voirin, Bernard
, p. 1211 - 1214 (1995)
Besides rutin, quercetin 3-rhamnoside and kaempferol 3-rhamnosyl (1-4)galactoside, and 1,6,8-trihydroxy-1-methyl anthraquinone (emodine) have been characterized from leaves of Rumex chalepensis.The structures were established on the basis of Rf values, acid hydrolysis to aglycone and sugar and UV, EI and FAB-mass-spectra, 1H NMR, 12C DEPT NMR, NOE difference measurements, 1H-H-COSY and 1H-13C COSY spectral data.
Mechanistically elucidating the in vitro safety and efficacy of a novel doxorubicin derivative
Alrushaid, Samaa,Zhao, Yunqi,Sayre, Casey L.,Maayah, Zaid H.,Laird Forrest,Senadheera, Sanjeewa N.,Chaboyer, Kevin,Anderson, Hope D.,El-Kadi, Ayman O. S.,Davies, Neal M.
, p. 582 - 597 (2017)
Doxorubicin is an effective anticancer drug; however, it is cardiotoxic and has poor oral bioavazilability. Quercetin is a plant-based flavonoid with inhibitory effects on P-glycoprotein (P-gp) and CYP3A4 and also antioxidant properties. To mitigate these therapeutic barriers, DoxQ, a novel derivative of doxorubicin, was synthesized by conjugating quercetin to doxorubicin. The purpose of this study is to mechanistically elucidate the in vitro safety and efficacy of DoxQ. Drug release in vitro and cellular uptake by multidrug-resistant canine kidney (MDCK-MDR) cells were quantified by HPLC. Antioxidant activity, CYP3A4 inhibition, and P-gp inhibitory effects were examined using commercial assay kits. Drug potency was assessed utilizing triple-negative murine breast cancer cells, and cardiotoxicity was assessed utilizing adult rat and human cardiomyocytes (RL-14). Levels of reactive oxygen species and gene expression of cardiotoxicity markers, oxidative stress markers, and CYP1B1 were determined in RL-14. DoxQ was less cytotoxic to both rat and human cardiomyocytes and retained anticancer activity. Levels of ROS and markers of oxidative stress demonstrate lower oxidative damage induced by DoxQ compared to doxorubicin. DoxQ also inhibited the expression and catalytic activity of CYP1B1. Additionally, DoxQ inhibited CYP3A4 and demonstrated higher cellular uptake by MDCK-MDR cells than doxorubicin. DoxQ provides a novel therapeutic approach to mitigate the cardiotoxicity and poor oral bioavailability of doxorubicin. The cardioprotective mechanism of DoxQ likely involves scavenging ROS and CYP1B1 inhibition, while the mechanism of improving the poor oral bioavailability of doxorubicin is likely related to inhibiting CYP3A4 and P-gp.
Exploring the oxidation and iron binding profile of a cyclodextrin encapsulated quercetin complex unveiled a controlled complex dissociation through a chemical stimulus
Diamantis, Dimitrios A.,Ramesova, Sarka,Chatzigiannis, Christos M.,Degano, Ilaria,Gerogianni, Paraskevi S.,Karadima, Konstantina E.,Perikleous, Sonia,Rekkas, Dimitrios,Gerothanassis, Ioannis P.,Galaris, Dimitrios,Mavromoustakos, Thomas,Valsami, Georgia,Sokolova, Romana,Tzakos, Andreas G.
, p. 1913 - 1924 (2018)
Background: Flavonoids possess a rich polypharmacological profile and their biological role is linked to their oxidation state protecting DNA from oxidative stress damage. However, their bioavailability is hampered due to their poor aqueous solubility. This can be surpassed through encapsulation to supramolecular carriers as cyclodextrin (CD). A quercetin- 2HP-β-CD complex has been formerly reported by us. However, once the flavonoid is in its 2HP-β-CD encapsulated state its oxidation potential, its decomplexation mechanism, its potential to protect DNA damage from oxidative stress remained elusive. To unveil this, an array of biophysical techniques was used. Methods: The quercetin-2HP-β-CD complex was evaluated through solubility and dissolution experiments, electrochemical and spectroelectrochemical studies (Cyclic Voltammetry), UV–Vis spectroscopy, HPLC-ESI-MS/MS and HPLC-DAD, fluorescence spectroscopy, NMR Spectroscopy, theoretical calculations (density functional theory (DFT)) and biological evaluation of the protection offered against H2O2-induced DNA damage. Results: Encapsulation of quercetin inside the supramolecule's cavity enhanced its solubility and retained its oxidation profile. Although the protective ability of the quercetin-2HP-β-CD complex against H2O2 was diminished, iron serves as a chemical stimulus to dissociate the complex and release quercetin. Conclusions: We found that in a quercetin-2HP-β-CD inclusion complex quercetin retains its oxidation profile similarly to its native state, while iron can operate as a chemical stimulus to release quercetin from its host cavity. General significance: The oxidation profile of a natural product once it is encapsulated in a supramolecular carrier was unveiled as also it was discovered that decomplexation can be triggered by a chemical stimilus.
Elucidation of active site residues of Arabidopsis thaliana flavonol synthase provides a molecular platform for engineering flavonols
Chua, Chun Song,Biermann, Daniela,Goo, Kian Sim,Sim, Tiow-Suan
, p. 66 - 75 (2008)
Arabidopsis thaliana flavonol synthase (aFLS) catalyzes the production of quercetin, which is known to possess multiple medicinal properties. aFLS is classified as a 2-oxoglutarate dependent dioxygenase as it requires ferrous iron and 2-oxoglutarate for catalysis. In this study, the putative residues for binding ferrous iron (H221, D223 and H277), 2-oxoglutarate (R287 and S289) and dihydroquercetin (H132, F134, K202, F293 and E295) were identified via computational analyses. To verify the proposed roles of the identified residues, 15 aFLS mutants were constructed and their activities were examined via a spectroscopic assay designed in this study. Mutations at H221, D223, H277 and R287 completely abolished enzymes activities, supporting their importance in binding ferrous iron and 2-oxoglutarate. However, mutations at the proposed substrate binding residues affected the enzyme catalysis differently such that the activities of K202 and F293 mutants drastically decreased to approximately 10% of the wild-type whereas the H132F mutant exhibited approximately 20% higher activity than the wild-type. Kinetic analyses established an improved substrate binding affinity in H132F mutant (Km: 0.027 ± 0.0028 mM) compared to wild-type (Km: 0.059 ± 0.0063 mM). These observations support the notion that aFLS can be selectively mutated to improve the catalytic activity of the enzyme for quercetin production.
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Neshta et al.
, (1972)
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One-pot preparation of quercetin using natural deep eutectic solvents
Zang, Yuan-Yuan,Yang, Xi,Chen, Zhi-Gang,Wu, Tao
, p. 193 - 198 (2020)
In this study, we have established a green and efficient preparation method of quercetin. Rutin was first extracted from Sophora japonica using natural deep eutectic solvents (NADESs), then hydrolyzed into quercetin by rutin degrading enzyme (RDE) obtained from germinated tartary buckwheat in situ. Rutin solubility tests showed that most of the 11 NADESs increased the solubility of rutin by 67-3116 times compared to water. Thus, NADESs could be prior candidate to extract rutin. Extraction efficiency of rutin varied with different NADESs, and a maximum of 291.57 mg g?1 was achieved in NADES ChGly, which was prepared by mixing choline chloride and glycerol at a molar ratio of 1:1. After that hydrolysis was performed directly in extraction system by adding RDE with degradation rate of up to 8.36 mg min-1·L-1. Our findings suggest that preparation of quercetin using NADESs was simple and feasible to operate, environmentally friendly, efficient, and inspired the preparation method of bioactive components from a new perspective.
Quercetin galactoside gallate in Euphorbiaceae
Nahrstedt,Dumkow,Janistyn,Pohl
, p. 559 - 562,561,562 (1974)
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Zakharov et al.
, (1970)
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Flavonoids from Teucrium orientale
Oganesyan
, (2013)
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Chumbalov,Mukhamed'yarova
, (1969)
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Flavonoids from Calendula officinalis flowers
Kurkin,Sharova
, p. 216 - 217 (2007)
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Zurabishvili
, (1974)
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Involvement of rat cytochrome 1A1 in the biotransformation of kaempferol to quercetin: Relevance to the genotoxicity of kaempferol
Duarte Silva,Rodrigues,Gaspar,Maia,Laires,Rueff
, p. 383 - 390 (1997)
Kaempferol is a flavonoid widely distributed in edible plants and has been shown to be genotoxic to V79 cells in the absence of external metabolizing systems. The presence of an external metabolizing system, such as rat liver homogenates (S9 mix), leads to an increase in its genotoxicity, which is attributed to its biotransformation to the more genotoxic flavonoid quercetin, via the cytochrome P450 (CYP) mono-oxygenase system. In the present work we investigated the mechanisms of the genotoxicity of kaempferol further. Special attention has been given to the role of CYP in the genotoxicity of this flavonoid. We studied the induction of mutations in Salmonella typhimurium TA98 in the presence and in the absence of S9 mix and the induction of chromosomal aberrations (CAs) and micronuclei (MN) by kaempferol in V79 cells in the presence and in the absence of S9 mix. To evaluate the role of different CYP in the biotransformation of kaempferol we studied the induction of CAs and MN in V79 cells genetically engineered for the expression of rat CYP 1A1, 1A2 and 2B1. In addition we performed CYP inhibition studies using the above-mentioned indicators and high performance liquid chromatography (HPLC) analysis. The results obtained in this work suggest that rat CYP 1A1 is, among the cytochromes studied, the one that plays the major role in the transformation of kaempferol into quercetin. The relevance of these findings to the human situation is discussed.
Hydrolysis of flavonoid glycosides by propolis β-glycosidase
Zhang, Cui-Ping,Liu, Gang,Hu, Fu-Liang
, p. 270 - 273 (2012)
Flavonoids generally occur as O-glycosides with sugars bound in nature, while aglycones and their derivatives are the main flavonoids in propolis. The objective of this work was to study the propolis β-glycosidase activities toward flavonoid β-glycosides and their conjugated forms. β-Glycosidase was extracted from propolis, incubated with avonoid glycosides, and analysed for aglycone formation by HPLC. The results demonstrated that glucose conjugates were rapidly hydrolysed, but not conjugates with other sugars, i.e. rutin and naringin. The rate and extent of deglycosylation depends on the structure of the avonoid and the position of the sugar substituitions. Quercetin 3-O-glucoside had the highest percent of hydrolysis, while quercetin 7-O-glucoside was the least hydrolysed. The Km values for hydrolysis of apigenin 7-glucoside and luteolin-7-O-glucoside were 13M and 20M, respectively.
Transformation of rutin to antiproliferative quercetin-3-glucoside by aspergillus niger
Ju You, Hyun,Jin Ahn, Hyung,Ji, Geun Eog
, p. 10886 - 10892 (2010)
The flavonol quercetin in plants and foods occurs predominantly in the form of glycoside whose sugar moiety affects the bioavailability and the mechanism of its biological activities. The antiproliferative activities of quercetin derivatives such as quercetin aglycone, quercetin-3-ss-D-glucoside (Q3G), and rutin were compared using six different cancer cell lines including colon, breast, hepatocellular, and lung cancer. The IC50 value of Q3G ranged between 15 and 25 μM in HT-29, HCT 116, MCF-7, HepG2, and A549 cells. In these five cell lines, Q3G showed the most potent growth inhibition, whereas rutin showed the least potency. Transformation of rutin to Q3G was conducted by controlling R-L-rhamnosidase and ss-D-glucosidase activities from crude enzyme extract of Aspergillus niger. Carbon sources during culture and transformation conditions such as pH, temperature, and heatstability were optimized. After 4 h biotransformation, 99% of rutin was transformed to Q3G and no quercetin was detected. This study presented an efficient biotransformation for the conversion of rutin to Q3G which was newly shown to have more potent antiproliferative effect than quercetin and rutin. 2010 American Chemical Society.
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Gumenyuk et al.
, (1972)
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Azimov,Nazirov
, (1970)
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Nuralieva et al.
, (1969)
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Batyuk,Kol'tsova
, (1968)
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Flavonoids from Gossypium hirsutum flowers
Wu,Abdulla,Yang,Aisa
, p. 370 - 371 (2008)
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Maksyutina
, (1967)
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Isolation, characterization, complete structural assignment, and anticancer activities of the methoxylated flavonoids from rhamnus disperma roots
Abd El-Wahab, Mohammed F.,Abdalla, Ashraf N.,Mohammed, Abd El-Salam I.,Mohammed, Hamdoon A.,Ragab, Ehab A.,Shaheen, Usama
, (2021/10/01)
Different chromatographic methods including reversed-phase HPLC led to the isolation and purification of three O-methylated flavonoids; 5,4’-dihydroxy-3,6,7-tri-O-methyl flavone (penduletin) (1), 5,3’-dihydroxy-3,6,7,4’,5’-penta-O-methyl flavone (2), and 5-hydroxy-3,6,7,3’,4’,5’-hexa-O-methyl flavone (3) from Rhamnus disperma roots. Additionlly, four flavonoid glycosides; kampferol 7-O-α-L-rhamnopyranoside (4), isorhamnetin-3-O-β-D-glucopyranoside (5), quercetin 7-O-α-L-rhamnopyranoside (6), and kampferol 3, 7-di-O-α-L-rhamnopyranoside (7) along with benzyl-O-β-D-glucopyranoside (8) were successfully isolated. Complete structure characterization of these compounds was assigned based on NMR spectroscopic data, MS analyses, and comparison with the literature. The O-methyl protons and carbons of the three O-methylated flavonoids (1–3) were unambiguously assigned based on 2D NMR data. The occurrence of compounds 1, 4, 5, and 8 in Rhamnus disperma is was reported here for the first time. Compound 3 was acetylated at 5-OH position to give 5-O-acetyl-3,6,7,3’,4’,5’-hexa-O-methyl flavone (9). Compound 1 exhibited the highest cytotoxic activity against MCF 7, A2780, and HT29 cancer cell lines with IC50 values at 2.17 μM, 0.53 μM, and 2.16 μM, respectively, and was 2–9 folds more selective against tested cancer cell lines compared to the normal human fetal lung fibroblasts (MRC5). It also doubled MCF 7 apoptotic populations and caused G1 cell cycle arrest. The acetylated compound 9 exhibited cytotoxic activity against MCF 7 and HT29 cancer cell lines with IC50 values at 2.19 μM and 3.18 μM, respectively, and was 6–8 folds more cytotoxic to tested cancer cell lines compared to the MRC5 cells.