chrysin has been researched along with fisetin* in 9 studies
9 other study(ies) available for chrysin and fisetin
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Inhibition of amyloid fibrillation of apo-carbonic anhydrase by flavonoid compounds.
Flavonoids are polyphenol compounds abundantly found in plants and reported to have an inhibitory effect on amyloid fibrillation. The number and position of hydroxyl groups, as well as the arrangement of flavonoids rings, may influence their inhibitory effects. In this study, we investigate the effect of structural characteristics of flavonoids on amyloid fibril formation. For this purpose, five compounds (i.e., biochanin A, daidzein, quercetin, chrysin and fisetin) were selected that represent a variety in the number and position of their hydroxyl groups. The inhibitory effect of these flavonoids on the amyloid fibril formation of apo-carbonic anhydrase (apo-BCA), as a model protein, was evaluated using thioflavin T and transmission electron microscopy. The results showed that fisetin possessed the most significant inhibitory effect. Interestingly, upon apo-BCA acetylation, none of the tested flavonoids could inhibit the fibrillation process, which indicates that the interactions of these compounds with the amine groups of lysine residues could be somewhat important. Topics: Acetylation; Amyloidogenic Proteins; Apoproteins; Benzothiazoles; Carbonic Anhydrases; Flavonoids; Flavonols; Fluorescent Dyes; Genistein; Isoflavones; Quercetin; Solutions; Structure-Activity Relationship | 2019 |
Inhibitory potential of flavonoids on PtdIns(3,4,5)P3 binding with the phosphoinositide-dependent kinase 1 pleckstrin homology domain.
Many membrane-associated proteins are involved in various signaling pathways, including the phosphoinositide 3-kinase (PI3K) pathway, which has key roles in diverse cellular processes. Disruption of the activities of these proteins is involved in the development of disease in humans, making these proteins promising targets for drug development. In most cases, the catalytic domain is targeted; however, it is also possible to target membrane associations in order to regulate protein activity. In this study, we established a novel method to study protein-lipid interactions and screened for flavonoid-derived antagonists of PtdIns(3,4,5)P Topics: 3-Phosphoinositide-Dependent Protein Kinases; Binding Sites; Flavones; Flavonoids; Flavonols; Liposomes; Molecular Docking Simulation; Phosphatidylinositol Phosphates; Pleckstrin Homology Domains; Protein Binding; Quantitative Structure-Activity Relationship | 2017 |
Molecular dynamic behavior and binding affinity of flavonoid analogues to the cyclin dependent kinase 6/cyclin D complex.
The cyclin dependent kinases (CDKs), each with their respective regulatory partner cyclin that are involved in the regulation of the cell cycle, apoptosis, and transcription, are potentially interesting targets for cancer therapy. The CDK6 complex with cyclin D (CDK6/cycD) drives cellular proliferation by phosphorylation of specific key target proteins. To understand the flavonoids that inhibit the CDK6/cycD functions, molecular dynamics simulations (MDSs) were performed on three inhibitors, fisetin (FST), apigenin (AGN), and chrysin (CHS), complexed with CDK6/cycD, including the two different binding orientations of CHS: FST-like (CHS_A) and deschloro-flavopiridol-like (CHS_B). For all three inhibitors, including both CHS orientations, the conserved interaction between the 4-keto group of the flavonoid and the backbone V101 nitrogen of CDK6 was strongly detected. The 3'- and 4'-OH groups on the flavonoid phenyl ring and the 3-OH group on the benzopyranone ring of inhibitor were found to significantly increase the binding and inhibitory efficiency. Besides the electrostatic interactions, especially through hydrogen bond formation, the van der Waals (vdW) interactions with the I19, V27, F98, H100, and L152 residues of CDK6 are also important factors in the binding efficiency of flavonoids against the CDK6/cycD complex. On the basis of the docking calculation and MM-PBSA method, the order of the predicted inhibitory affinities of these three inhibitors toward the CDK6/cycD was FST > AGN > CHS, which is in good agreement with the experimental data. In addition, CHS preferentially binds to the active CDK6 in a different orientation to FST and AGN but similar to its related analog, deschloro-flavopiridol. The obtained results are useful as the basic information for the further design of potent anticancer drugs specifically targeting the CDK6 enzyme. Topics: Antineoplastic Agents, Phytogenic; Apigenin; Binding Sites; Crystallography, X-Ray; Cyclin D; Cyclin-Dependent Kinase 6; Flavonoids; Flavonols; Humans; Hydrogen Bonding; Molecular Conformation; Molecular Dynamics Simulation; Piperidines; Protein Binding; Static Electricity; Thermodynamics | 2012 |
Protection of burn-induced skin injuries by the flavonoid kaempferol.
Thermal burn injury induces inflammatory cell infiltrates in the dermis and thickening of the epidermis. Following a burn injury, various mediators, including reactive oxygen species (ROS), are produced in macrophages and neutrophils, exposing all tissues to oxidative injury. The anti-oxidant activities of flavonoids have been widely exploited to scavenge ROS. In this study, we observed that several flavonoids-kaempferol, quercetin, fisetin, and chrysin-inhibit LPS-induced IL-8 promoter activation in RAW 264.7 cells. In contrast with quercetin and fisetin, pretreatment of kaempferol and chrysin did not decrease cell viability. Inflammatory cell infiltrates in the dermis and thickening of the epidermis induced by burn injuries in mice was relieved by kaempferol treatment. However, the injury was worsened by fisetin, quercetin, and chrysin. Expression of TNF-a induced by burn injuries was decreased by kaempferol. These findings suggest the potential use of kaempferol as a therapeutic in thermal burn-induced skin injuries. [BMB reports 2010; 43(1): 46-51]. Topics: Animals; Burns; Cell Differentiation; Cell Line, Tumor; Flavonoids; Flavonols; Interleukin-8; Kaempferols; Lipopolysaccharides; Mice; Quercetin; Reactive Oxygen Species; Skin; Tumor Necrosis Factor-alpha | 2010 |
Crystal structure of a human cyclin-dependent kinase 6 complex with a flavonol inhibitor, fisetin.
Cyclin-dependent kinases (CDKs) play a central role in cell cycle control, apoptosis, transcription, and neuronal functions. They are important targets for the design of drugs with antimitotic or antineurodegenerative effects. CDK4 and CDK6 form a subfamily among the CDKs in mammalian cells, as defined by sequence similarities. Compared to CDK2 and CDK5, structural information on CDK4 and CDK6 is sparse. We describe here the crystal structure of human CDK6 in complex with a viral cyclin and a flavonol inhibitor, fisetin. Fisetin binds to the active form of CDK6, forming hydrogen bonds with the side chains of residues in the binding pocket that undergo large conformational changes during CDK activation by cyclin binding. The 4-keto group and the 3-hydroxyl group of fisetin are hydrogen bonded with the backbone in the hinge region between the N-terminal and C-terminal kinase domain, as has been observed for many CDK inhibitors. However, CDK2 and HCK kinase in complex with other flavone inhibitors such as quercetin and flavopiridol showed a different binding mode with the inhibitor rotated by about 180 degrees. The structural information of the CDK6-fisetin complex is correlated with the binding affinities of different flavone inhibitors for CDK6. This complex structure is the first description of an inhibitor complex with a kinase from the CDK4/6 subfamily and can provide a basis for selecting and designing inhibitor compounds with higher affinities and specificities. Topics: Binding Sites; Crystallization; Crystallography, X-Ray; Cyclin-Dependent Kinase 5; Cyclin-Dependent Kinase 6; Cyclin-Dependent Kinases; Cyclins; Flavonoids; Flavonols; Humans; Ligands; Models, Molecular; Molecular Structure; Protein Binding; Structure-Activity Relationship | 2005 |
Inhibitory effects of some flavonoids on the activity of mushroom tyrosinase.
Mushroom tyrosinase (EC 1.14.18.1) is a copper containing oxidase that catalyzes both the hydroxylation of tyrosine into o-diphenols and the oxidation of o-diphenols into o-quinones, and then forms brown or black pigments. In the present study, the effects of some flavonoids on the oxidation of L-3,4-dihydroxyphenylalanine (L-DOPA) have been studied. The results show that flavonoids can lead to reversible inhibition of the enzyme. A kinetic analysis showed that the flavonols are competitive inhibitors, whereas luteolin is an uncompetitive inhibitor. The rank order of inhibition was: quercetin > galangin > morin; fisetin > 3,7,4;-trihydroxyflavone; luteolin > apigenin > chrysin. Topics: Agaricales; Apigenin; Binding, Competitive; Catalysis; Copper; Dose-Response Relationship, Drug; Enzyme Inhibitors; Flavonoids; Flavonols; Kinetics; Luteolin; Models, Chemical; Molecular Structure; Monophenol Monooxygenase; Quercetin; Rutin; Structure-Activity Relationship | 2003 |
Relaxation to flavones and flavonols in rat isolated thoracic aorta: mechanism of action and structure-activity relationships.
The mechanism of the relaxant action and the structure-activity relation of flavonols (fisetin, quercetin, and 3,3',4'-trihydroxyflavone) and flavones (apigenin, chrysin, and luteolin) were examined in rat isolated thoracic aorta. The control responses to flavonols and flavones were compared with responses observed after the removal of the endothelium or in the presence of the L-type Ca2+ channel blocker, nifedipine (10(-7) M). The effects of flavonoids on contraction caused by the influx of extracellular Ca2+ and agonist-induced release of intracellular Ca2+ also were investigated. The flavones exhibited endothelium-independent vasorelaxation, whereas the removal of the endothelium significantly decreased the sensitivity of the relaxant responses to the flavonols without affecting the maximal relaxation. In the presence of nifedipine, the responses to apigenin, luteolin, and quercetin were significantly inhibited, but relaxation to chrysin, fisetin, and 3,3',4'-trihydroxyflavone was unaffected. All flavonols and flavones caused concentration-dependent inhibition of the contractile responses to exogenous application of Ca2+ and the release of intracellular Ca2+ stimulated by phenylephrine. Of the six flavonoids examined, 3,3',4'-trihydroxyflavone was the most potent when causing vasorelaxation or inhibition of contraction caused by the influx or release of Ca2+. In conclusion, these studies provide evidence that the hydroxyl substitution in the carbon 3 position that characterizes the flavonols is important in stimulating endothelium-dependent vasorelaxation, and the absence of hydroxyl substitution on the A phenolic ring enhances the relaxant action. Topics: Animals; Aorta, Thoracic; Apigenin; Calcium; Dose-Response Relationship, Drug; Drug Interactions; Endothelium, Vascular; Flavonoids; Flavonols; In Vitro Techniques; Luteolin; Male; Muscle Relaxation; Muscle, Smooth, Vascular; Nifedipine; Phenylephrine; Quercetin; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship | 2000 |
Sulphation of resveratrol, a natural compound present in wine, and its inhibition by natural flavonoids.
1. Resveratrol, a polyphenolic compound present in grape and wine, has beneficial effects against cancer and protective effects on the cardiovascular system. Resveratrol is sulphated, and the hepatic and duodenal sulphation might limit the bioavailability of this compound. The aim of this study was to see whether natural flavonoids present in wine, fruits and vegetables inhibit the sulphation of resveratrol in the human liver and duodenum. 2. In the liver, IC50 for the inhibition of resveratrol sulphation was 12+/-2 pM (quercetin), 1.0+/-0.04 microM (fisetin), 1.4+/-0.1 microM (myricetin), 2.2+/-0.1 microM (kaempferol) and 2.8+/-0.2 microM (apigenin). Similarly, in the duodenum, IC50 was 15+/-2 pM (quercetin), 1.3+/-0.1 microM (apigenin), 1.3+/-0.5 microM (fisetin), 2.3+/-0.1 microM (kaempferol) and 2.5+/-0.3 microM (myricetin). 3. The type of inhibition of quercetin on resveratrol sulphation was studied in three liver samples and was determined to be non-competitive and mixed in nature. Km (mean+/-SD; microM) was 0.23+/-0.07 (control), 0.40+/-0.08 (5 pM quercetin) and 0.56+/-0.09 (10 pM quercetin). Vmax (mean+/-SD; pmol min(-1) x mg(-1)) was 99+/-11 (control), 73+/-15 (5 pM quercetin) and 57 +/- 10 (10 pM quercetin). Kj and Kies estimates (mean+/-SD) were 3.7+/-1.8 pM and 12.1+/-1.7 pM respectively (p = 0.010). 4. Chrysin was a substrate for the sulphotransferase(s) and an assay was developed for measuring the chrysin sulphation rate in human liver. The enzyme followed Michaelis-Menten kinetics and Km and Vmax (mean+/-SD) measured in four livers were 0.29+/-0.07 microM and 43.1+/-1.9 pmol x min(-1) x mg(-1) respectively. 5. Catechin was neither an inhibitor of resveratrol sulphation nor a substrate of sulphotransferase. 6. These results are consistent with the view that many, but not all, flavonoids inhibit the hepatic and duodenal sulphation of resveratrol, and such inhibition might improve the bioavailability of this compound. Topics: Aged; Apigenin; Biological Availability; Duodenum; Female; Flavonoids; Flavonols; Fruit; Humans; Kaempferols; Kinetics; Liver; Male; Middle Aged; Quercetin; Resveratrol; Stilbenes; Substrate Specificity; Sulfates; Sulfotransferases; Vegetables; Wine | 2000 |
Inhibition by flavonoids of RNA synthesis in permeable WI-38 cells and of transcription by RNA polymerase II.
The effects of various flayonoids on RNA synthesis in permeable human fibroblasts or on transcription with mouse RNA polymerase II were studied. Quercetin or kaempferol inhibited transcription in permeable cells but flavone did so only slightly. In the transcription of naked DNA with purified RNA polymerase II, mutagenic quercetin, kaempferol or fisetin strongly inhibited the reaction but non-mutagenic or weakly mutagenic flavone and chrysin inhibited it only weakly. Quercetin seems to inhibit the transcription by interaction with the enzyme. Topics: Animals; Cell Line; Cell Membrane Permeability; DNA Replication; Flavones; Flavonoids; Flavonols; Humans; Kaempferols; Kinetics; Mice; Quercetin; RNA Polymerase II; Structure-Activity Relationship; Transcription, Genetic | 1984 |