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Seven previously undescribed flavonol glycosides including four rare flavonol glycoside cyclodimers, dicyclopaliosides A-C (1-3) with truxinate type and dicyclopalioside D (4) with truxillate type, as well as three kaempferol glycoside derivatives cyclopaliosides A-C (5-7), were obtained from the leaves of Cyclocarya paliurus. Their structures were elucidated by extensive spectroscopic methods and chemical analyses. All compounds were evaluated for their inhibitory α-glucosidase activities. Among them, compounds 1-4 display strong inhibitory activities with IC 50 values of 82.76 ± 1.41, 62.70 ± 4.00, 443.35 ± 16.48, and 6.31 ± 0.88 nM, respectively, while compounds 5-7 showed moderate activities with IC 50 values of 4.91 ± 0.75, 3.64 ± 0.68, and 5.32 ± 0.53 μΜ, respectively. The structure-activity relationship analysis assumed that the cyclobutane cores likely contribute to the enhancement of α-glucosidase inhibitory activities of dimers. Also, the interaction mechanism between flavonol glycoside dimers and α-glucosidase were explored by the enzyme kinetic assay, indicating that compounds 1-3 exhibited mixed-type inhibition, while 4 showed uncompetitive inhibition. Additionally, the active compounds have also undergone molecular docking evaluation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Wet synthesis approach afforded four new heteroleptic mononuclear neutral diamagnetic oxidovanadium(V) complexes, comprising salicylaldehyde-based 2-furoic acid hydrazones and a flavonol coligand of the general composition [VO(fla)(L-ONO)]. The complexes were comprehensively characterized, including chemical analysis, conductometry, infrared, electronic, and mass spectroscopy, as well as 1D 1 H and proton-decoupled 13 C( 1 H) NMR spectroscopy, alongside extensive 2D 1 H 1 H COSY, 1 H 13 C HMQC, and 1 H 13 C HMBC NMR analyses. Additionally, the quantum chemical properties of the complexes were studied using Gaussian at the B3LYP, HF, and M062X levels on the 6-31++g(d,p) basis sets. The interaction of these hydrolytically inert vanadium complexes and the BSA was investigated through spectrofluorimetric titration, synchronous fluorimetry, and FRET analysis in a temperature-dependent manner, providing valuable thermodynamic insights into van der Waals interactions and hydrogen bonding. Molecular docking was conducted to gain further understanding of the specific binding sites of the complexes to BSA. Complex 2, featuring a 5-chloro-substituted salicylaldehyde component of the hydrazone, was extensively examined for its biological activity in vivo. The effects of complex administration on biochemical and hematological parameters were evaluated in both healthy and diabetic Wistar rats, revealing antihyperglycemic activity at millimolar concentration. Furthermore, histopathological analysis and bioaccumulation studies of the complex in the brain, kidneys, and livers of healthy and diabetic rats revealed the potential for further development of vanadium(V) hydrazone complexes as antidiabetic and insulin-mimetic agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Previously, we documented the synthesis and assessed the biological effects of chalcones containing selenium against HT-29 human colorectal adenocarcinoma cells, demonstrating their significant potential. As research on selenium-containing flavonoids remains limited, this article outlines our design and synthesis of three selenium-based flavonols and three 2-styrylchromones. We conducted evaluations of these compounds to determine their impact on human lung cancer cells (A549, H1975, CL1-0, and CL1-5) and their influence on normal lung fibroblast MRC5 cells. Additionally, we included selenium-based chalcones in our testing for comparative purposes. Our findings highlight that the simplest compound, designated as compound 1, exhibited the most promising performance among the tested molecules., (© 2024 Deutsche Pharmazeutische Gesellschaft.)

In this study, a series of novel hydrazide-containing flavonol derivatives was designed, synthesized, and evaluated for antifungal activity. In the in vitro antifungal assay, most of the target compounds exhibited potent antifungal activity against seven tested phytopathogenic fungi. In particular, compound C32 showed the best antifungal activity against Rhizoctonia solani (EC 50 = 0.170 μg/mL), outperforming carbendazim (EC 50 = 0.360 μg/mL) and boscalid (EC 50 = 1.36 μg/mL). Compound C24 exhibited excellent antifungal activity against Valsa mali , Botrytis cinerea , and Alternaria alternata with EC 50 values of 0.590, 0.870, and 1.71 μg/mL, respectively. The in vivo experiments revealed that compounds C32 and C24 were potential novel agricultural antifungals. 3D quantitative structure-activity relationship (3D-QSAR) models were used to analyze the structure-activity relationships of these compounds. The analysis results indicated that introducing appropriate electronegative groups at position 4 of a benzene ring could effectively improve the anti- R. solani activity. In the antifungal mechanism study, scanning electron microscopy and transmission electron microscopy analyses revealed that C32 disrupted the normal growth of hyphae by affecting the structural integrity of the cell membrane and cellular respiration. Furthermore, compound C32 exhibited potent succinate dehydrogenase (SDH) inhibitory activity (IC 50 = 8.42 μM), surpassing that of the SDH fungicide boscalid (IC 50 = 15.6 μM). The molecular dynamics simulations and docking experiments suggested that compound C32 can occupy the active site and form strong interactions with the key residues of SDH. Our findings have great potential for aiding future research on plant disease control in agriculture.

Flavonoids epitomize structural scaffolds in many biologically active synthetic and natural compounds. They showcase a diverse spectrum of biological activities including anticancer, antidiabetic, antituberculosis, antimalarial, and antibiofilm activities. The antibiofilm activity of a series of new chalcones and flavonols against clinically significant Pseudomonas aeruginosa PAO1 strain was studied. Antivirulence activities were screened by analysing the effect of compounds on the production of virulence factors like pyocyanin, LasA protease, cell surface hydrophobicity, and rhamnolipid. The best ligands towards the quorum sensing proteins LasR, RhlR, and PqsR were recognised using a molecular docking study. The gene expression in P. aeruginosa after treatment with test compounds was evaluated on quorum sensing genes including rhlA, lasB, and pqsE. The antibiofilm potential of chalcones and flavonols was confirmed by the efficient reduction in the production of virulence factors and downregulation of gene expression., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Alzheimer's disease (AD) is a neurodegenerative disorder marked by cognitive impairment and memory loss. In this study, AD was experimentally induced in rats using aluminum chloride (AlCl 3 ) and D-galactose (D-gal). Fisetin (Fis), a natural compound with antioxidant and anti-inflammatory properties, has potential for neurodegeneration management, but its low bioavailability limits clinical applications. To address this, we synthesized and characterized Pluronic-2-Acrylamido-2-methylpropane sulfonic acid (PLUR-PAMPS) nanogels using gamma radiation and successfully loaded Fis onto them (Fis-PLUR-PAMPS). The optimal formulation exhibited minimal particle size, a highly acceptable polydispersity index, and the highest zeta-potential, enhancing stability and solubilization efficiency. Our goal was to improve Fis's bioavailability and assess its efficacy against AlCl 3 /D-gal-induced AD. Male albino Wistar rats were pre-treated orally with Fis (40 mg/kg) or Fis-PLUR-PAMPS for seven days, followed by a seven-day intraperitoneal injection of AlCl 3 and D-gal. Behavioral assessments, histopathological analysis, and biochemical evaluation of markers related to AD pathology were conducted. Results demonstrated that Fis-PLUR-PAMPS effectively mitigated cognitive impairments and neurodegenerative signs induced by AlCl 3 /D-gal. These findings suggest that Fis-PLUR-PAMPS nanogels enhance Fis's bioavailability and therapeutic efficacy, offering a promising approach for AD management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

An oxidising and substituting one-pot reaction strategy has been developed to synthesise dihydromyricetin derivatives with the aim of enhancing the inhibitory activity of dihydromyricetin against SARS-CoV-2. Different ω -methoxy- ω -oxeylkyl was introduced in C 7 -OH site and yielded eight analogs, all of them showed good inhibitory activity against SARS-CoV-2 3CL pro with IC 50 values ranging from 0.72 to 2.36 μM. In the Vero E6-cell, compound 3 has a good activity of anti-SARS-CoV-2 virus (Omicron virus BA.5) in the prevention model, with an EC 50 of 15.84 μM, and so do compound 10 in the therapeutic model, with an EC 50 of 11.52 μM. The results suggest that the introduction of long chain ω -oxeylkyl at C 7 -OH facilitate the inhibition of viral replication in the therapeutic model, which is consistent with the binding energies predicted from molecular docking conclusions. It implies that dihydromyricetin derivatives have the potential to become effective inhibitors of SARS-CoV-2 Omicron and other viruses.

In this work, effects of cellulose nanofiber/dihydromyricetin (CNF/DMY) ratio on the structural, antioxidant and emulsifying properties of the CNF/DMY mixtures were investigated. CNF integrated with DMY via hydrogen bonding and the antioxidant capacity of mixtures increased with decreasing CNF/DMY ratio (k). The oxidative stability of emulsions enhanced as the DMY content increased. Emulsions formed at Φ = 0.5 displayed larger size (about 25 μm), better viscoelasticity and centrifugal stability than those at Φ = 0.3 (about 23 μm). The emulsions at k = 17:3 and Φ = 0.5 exhibited the most excellent viscoelasticity. In conclusion, the DMY content in mixtures and the oil phase fraction exhibited distinct synergistic effects on the formation and characteristics of emulsions, and the emulsions could demonstrate superior oxidative and storage stability. These findings could provide a novel strategy to extend the shelf life of cellulose-based emulsions and related products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Flavonol glycosides, contributing to the health benefits and distinctive flavors of tea ( Camellia sinensis ), accumulate predominantly as diglycosides and triglycosides in tea leaves. However, the UDP-glycosyltransferases (UGTs) mediating flavonol multiglycosylation remain largely uncharacterized. In this study, we employed an integrated proteomic and metabolomic strategy to identify and characterize key UGTs involved in flavonol triglycoside biosynthesis. The recombinant rCsUGT75AJ1 exhibited flavonoid 4'- O -glucosyltransferase activity, while rCsUGT75L72 preferentially catalyzed 3-OH glucosylation. Notably, rCsUGT73AC15 displayed substrate promiscuity and regioselectivity, enabling glucosylation of rutin at multiple sites and kaempferol 3- O -rutinoside (K3R) at the 7-OH position. Kinetic analysis revealed rCsUGT73AC15's high affinity for rutin ( K m = 9.64 μM). Across cultivars, CsUGT73AC15 expression inversely correlated with rutin levels. Moreover, transient CsUGT73AC15 silencing increased rutin and K3R accumulation while decreasing their respective triglycosides in tea plants. This study offers new mechanistic insights into the key roles of UGTs in regulating flavonol triglycosylation in tea plants.

Carbon monoxide (CO) delivery molecules are of significant current interest as potential therapeutics, including for anticancer applications. A recent approach toward generating new types of materials-based anticancer agents involves combining the Fenton reactivity of a redox active metal ion with CO delivery. However, small molecule examples of these types of entities have not been systematically studied to evaluate the combined effect on cellular toxicity. Herein we describe a Cu(II) flavonolato complex which produces anticancer effects through a combination of copper-mediated reactive oxygen species (ROS) generation and light-induced flavonol CO release. Confocal microscopy studies provide evidence of enhanced flavonol uptake in the copper flavonolato system relative to the free flavonol, which leads to an increased amount of CO delivery within cells. Importantly, this work demonstrates that a metal flavonolato species can be used to produce enhanced toxicity effects resulting from both metal ion-induced Fenton reactivity and increased cellular uptake of a flavonol CO donor., (© 2024 Wiley-VCH GmbH.)

This study aims to investigate the impact of four key factors, namely, temperature, water source, metal ion, and pH, on the stability of molecular chirality of dihydromyricetin (DMY) and proposed effective strategies for configuration protection. The findings reveal that temperatures exceeding 80°C could accelerate the racemization process of DMY, with a significant increase in racemization observed at 100°C. In addition, DMY exhibited heightened stability in ultrapure water as compared to various water sources, including pure water-1, pure water-2, mineral water, and running water. Notably, the presence of Fe 2+ displayed an inhibitory effect on the racemization of DMY, whereas Mg 2+ , Ca 2+ , and Mn 2+ showed a substantial promotional effect. Additionally, acidic conditions (pH < 5.0) were found to be protective for maintaining the stability of DMY, whereas alkaline conditions (pH > 9.0) were observed to be detrimental. Meanwhile, we first identified the presence of another pair of DMY isomers in this work., (© 2024 Institute of Food Technologists.)

This study explores the coordination dynamics between dietary polyphenols, specifically kaempferol, quercetin, and myricetin, and Cu ions in aqueous environments. A novel synthesis method for flavonol-Cu(II) coordination compounds is introduced, effectively reducing interference from free metal ions. Our results reveal consistent binding patterns of Cu ions with flavonols (2:1 ratio of flavonol to Cu(II)), predominantly at the 4,5 sites. Various analytical techniques are used to validate these coordination ratios and sites. The binding affinity of the flavonols for Cu ions follows a descending sequence: myricetin > quercetin > kaempferol. Notably, coordination with Cu ions enhances the free-radical scavenging activities of these flavonols. These findings hold substantial importance for food chemistry, biology, and medicine, providing crucial insights into the way dietary flavonols form stable structures in environments similar to human body fluids and their interactions with metal ions, opening new possibilities for their application and understanding in diverse scientific domains., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Staphylea , also called bladdernuts, is a genus of plants belonging to the family Staphyleaceae, widespread in tropical or temperate climates of America, Europe, and the Far East. Staphylea spp. produce bioactive metabolites with antioxidant properties, including polyphenols which have not been completely investigated for their phytotherapeutic potential, even though they have a long history of use for food. Here, we report the isolation of six flavonol glycosides from the hydroalcoholic extract of aerial parts of Staphylea pinnata L., collected in Italy, using a solid-phase extraction technique. They were identified using spectroscopic, spectrometric, and optical methods as three quercetin and three isorhamnetin glycosides. Among the flavonol glycosides isolated, isoquercetin and quercetin malonyl glucoside showed powerful antioxidant, antimicrobial, and wound healing promoting activity and thus are valuable as antiaging ingredients for cosmeceutical applications and for therapeutic applications in skin wound repair.

Aronia melanocarpa berries contain many compounds with potential benefits for human health. The food flavonoids quercetin and rutin, found in significant amounts in the fruits of A. melanocarpa , are known to have favourable effects on animal and human organisms. However, data on the effect of flavonols isolated from black chokeberry on immune functions during immunosuppression are not available in the literature. Thus, the aim of this study was to evaluate the effect of flavonol fraction isolated from A. melanocarpa fruits, in comparison with pure quercetin and rutin substances, on the dysfunctional state of rat thymus and spleen in immunodeficiency. The study was performed on Wistar rats. The animals were orally administered solutions of the investigated substances for 7 days: water, a mixture of quercetin and rutin and flavonol fraction of A. melanocarpa . For induction of immunosuppression, the animals were injected once intraperitoneally with cyclophosphamide. Substance administration was then continued for another 7 days. The results showed that under the influence of flavonols, there was a decrease in cyclophosphamide-mediated reaction of lipid peroxidation enhancement and stimulation of proliferation of lymphocytes of thymus and spleen in rats. At that, the effect of the flavonol fraction of aronia was more pronounced.

To achieve the environmentally friendly and rapid green synthesis of efficient and stable AgNPs for drug-resistant bacterial infection, this study optimized the green synthesis process of silver nanoparticles (AgNPs) using Dihydromyricetin (DMY). Then, we assessed the impact of AgNPs on zebrafish embryo development, as well as their therapeutic efficacy on zebrafish infected with Methicillin-resistant Staphylococcus aureus (MRSA). Transmission electron microscopy (TEM) and dynamic light-scattering (DLS) analyses revealed that AgNPs possessed an average size of 23.6 nm, a polymer dispersity index (PDI) of 0.197 ± 0.0196, and a zeta potential of -18.1 ± 1.18 mV. Compared to other published green synthesis products, the optimized DMY-AgNPs exhibited smaller sizes, narrower size distributions, and enhanced stability. Furthermore, the minimum concentration of DMY-AgNPs required to affect zebrafish hatching and survival was determined to be 25.0 μg/mL, indicating the low toxicity of DMY-AgNPs. Following a 5-day feeding regimen with DMY-AgNP-containing food, significant improvements were observed in the recovery of the gills, intestines, and livers in MRSA-infected zebrafish. These results suggested that optimized DMY-AgNPs hold promise for application in aquacultures and offer potential for further clinical use against drug-resistant bacteria.

Mercury ion (Hg 2+ ) is one of harmful heavy metal ions that can accumulate inside the human organism and cause some health problems. In the article, a highly effective fluorescent probe named EC-T-PCBM was prepared by grafting flavonol derivatives onto ethyl cellulose for the specific recognition of Hg 2+ . EC-T-PCBM exhibited a remarkable fluorescence light-up response toward Hg 2+ with excellent sensitivity. EC-T-PCBM possessed several prominent sensing properties for Hg 2+ , such as low detection limit (43.9 nM), short response time (5 min), and wide detection pH range (6-9). The response mechanism of EC-T-PCBM to Hg 2+ has been verified through 1 H NMR titration and DFT computation. Additionally, EC-T-PCBM not only can be used for accurately determining trace amount of Hg 2+ in actual environmental water samples, but also can serve as a portable and rapid device by loading it on test strips for sensitive and selective visualization of Hg 2+ . More importantly, the confocal fluorescence imaging of onion cells suggested the favorable cell membrane permeability of EC-T-PCBM and its prominent ability to continuously monitor the enrichment from Hg 2+ within fresh plant tissues., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A series of flavanols were synthesized to assess their biological activity against human non-small cell lung cancer cells (A549). Among the sixteen synthesized compounds, it was observed that compounds 6k (3.14 ± 0.29 µM) and 6l (0.46 ± 0.02 µM) exhibited higher potency compared to 5-fluorouracil (5-Fu, 4.98 ± 0.41 µM), a clinical anticancer drug which was used as a positive control. Moreover, compound 6l (4'-bromoflavonol) markedly induced apoptosis of A549 cells through the mitochondrial- and caspase-3-dependent pathways. Consequently, compound 6l might be developed as a candidate for treating or preventing lung cancer.

Dihydromyricetin (DMY) was employed to reduce the yield of furfural derived from the Amadori rearrangement product of l-threonine and d-xylose (Thr-ARP) by trapping Thr-ARP, 3-deoxyxyosone (3-DX), and furfural to form adducts. The effect of different concentrations of DMY at different pH values and temperatures on the reduction of furfural production was studied, and the results showed that DMY could significantly reduce furfural production at higher pH (pH 5-7) and lower temperature (110 °C). Through the surface electrostatic potential analysis by Gaussian, a significant enhancement of the C 6 nucleophilic ability at higher pH (pH ≥ 5) was observed on DMY with hydrogen-dissociated phenol hydroxyl. The nucleophilic ability of DMY led to its trapping of Thr-ARP, 3-DX, and furfural with the generation of the adducts DMY-Thr-ARP, DMY-3-DX, and DMY-furfural. The formation of the DMY-Thr-ARP adduct slowed the degradation of Thr-ARP, caused the decrease of the 3-DX yield, and thereby inhibited the conversion of 3-DX to furfural. Therefore, DMY-Thr-ARP was purified, and the structure was identified by nuclear magnetic resonance (NMR). The results confirmed that C 6 or C 8 of DMY and carbonyl carbon in Thr-ARP underwent a nucleophilic addition reaction to form the DMY-Thr-ARP adduct. In combination with the analysis results of Gaussian, most of the DMY-Thr-ARP adducts were calculated to be C 6 -DMY-Thr-ARP. Furthermore, the formation of DMY-furfural caused furfural consumption. The formation of the adducts also shunted the pathway of both Thr-ARP and 3-DX conversion to furfural, resulting in a decrease in the level of furfural production.

In the field of thermal degradation of flavonoids, current studies mainly focused on flavonols. However, the thermal degradation of dihydroflavonols in aqueous solution has received limited attention compared to flavonols. The single C2-C3 bonds of dihydroflavonols, which differs from the C2-C3 double bond in flavonols, may cause different degradation mechanisms. Dihydromyricetin (DMY) is a typical dihydroflavonol with six hydroxyl groups, and possesses various health effects. We explored the thermal degradation of DMY in neutral aqueous solution (pH 7) at 100 ℃. Ultra-performance liquid chromatography combined with photodiode array and electrospray ionization quadrupole-time-of-flight tandem mass spectrometric detection (UPLC-PDA-ESI-QTOF-MS/MS) provided suitable platform for exploring DMY degradation pathways, and negative ion mode was applied. Thermal treatment led to a decline in DMY level with time, accompanied by the appearance of various degradation products of DMY. Degradation mechanisms of DMY included isomerization, oxidation, hydroxylation, dimerization and ring cleavage. The pyrogallol-type ring B of DMY might be initially oxidized into ortho-quinone, which could further attack another DMY to form dimers. In addition, hydroxylation is likely to occur at C-2, C-3 of DMY or DMY dimers, which then further yields ring-cleavage products via breakage of the O1-C2 bond, C2-C3 bond, or C3-C4 bond. The 3-hydroxy-5-(3,3,5,7-tetrahydroxy-4-oxochroman-2-yl) cyclohexa-3,5-diene-1, 2-dione (m/z 333.0244) and unknown compound m/z 435.0925 were annotated as key intermediates in DMY degradation. Four phenolic acids, including 3,4,5-trihydroxybenzoic acid (m/z 169.0136, RT 1.4 min), 2,4,6-trihydroxyphenylglyoxylic acid (m/z 197.0084, RT 1.7 min), 2-oxo-2-(2,4,6-trihydroxyphenyl) acetaldehyde (m/z 181.0132, RT 2.4 min), and 2,4,6-trihydroxybenzoic acid (m/z 169.0139, RT 2.5 min) were identified as the major end products of DMY degradation. In addition, 5-((3,5dihydroxyphenoxy) methyl)-3-hydroxycyclohexa-3,5-diene-1,2-dione (m/z 261.0399, RT 11.7 min) and unidentified compound with m/z 329.0507 (RT 1.0 min) were also suggested to be end products of DMY degradation. These results provide novel insights on DMY stability and degradation products. Moreover, the heat treatment of DMY aqueous solution was found to gradually reduce the antioxidant activities of DMY, and even destroy the beneficial effect of DMY on the gut microbiota composition., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Quercetin oxidation leads to the formation of a metabolite, 2-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxy-3(2H)-benzofuranone, whose antioxidant potency was recently reported to be a 1000-fold higher than that of its precursor. The formation of similar metabolites (BZF) is limited to certain flavonols (FL), among which are myricetin, fisetin, and morin. Here we addressed the consequences of inducing the auto-oxidation of these flavonols in terms of their antioxidant properties (assessed in ROS-exposed Caco-2 cells). The mixtures that result from their oxidation (FLox) exhibited antioxidant activities 10-to-50-fold higher than those of their precursors. Such amplification was fully attributable to the presence of BZF in each FLox (established by HPLC-ESI-MS/MS and chemical subtraction techniques). An identical amplification was also found when the antioxidant activities of BZF, isolated from each FLox, and FL were compared. These findings warrant the search of these BZF in edible plants and their subsequent evaluation as a new type of functional food ingredients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Flavonol and flavonoid compounds are important natural compounds with various biomedical activities. Therefore, it is of great significance to develop a strategy for the specific extraction of flavonol and flavonoid compounds. Quercetin is a well-studied flavonoid possessing many health benefits. This compound is a versatile antioxidant known to possess protective abilities against body tissue injury induced by pathological situations and various drug toxicities. Although quercetin is widely distributed in many plants, its content generally is not very high. Therefore, the specific extraction of quercetin as well as other flavonol and flavonoid compounds has profound significance. In this work, the quercetin molecularly imprinting polymer (QMIP) was successfully prepared, in which a typical flavonol quercetin was selected as the template molecule. QMIP was synthesized by performing the surface molecular imprinting technology on the surface of NH 2 -MIL-101(Fe). Our study results showed that QMIP exhibited quick binding kinetic behavior, a high adsorption capacity (57.04[Formula: see text]mg/g), and the specific recognition ability toward quercetin compared with structurally distinct compounds (selective [Formula: see text]). The specific adsorption ability of quercetin by QMIP was further explained using computation simulation that molecules with non-planar 3D conformations hardly entered the molecularly imprinted cavities on QMIP. Finally, QMIP was successfully used for the specific extraction of quercetin and five other flavonol and flavonoid compounds in the crude extracts from Sapium sebiferum . This study proposes a new strategy to synthesize the molecularly imprinted polymer based on a single template for enriching and loading a certain class of active ingredients with similar core structures from variable botanicals.

In this work, four structurally similar flavonols (galangin, kaempferol, quercetin and myricetin) were coated on the surface of (11-mercaptoundecyl)-N,N,N-trimethylammonium bromide (MUTAB)‑gold nanoparticles (AuNPs) by two-step phase transfer and self-assembly, and the cationic MUTAB- AuNPs coated with flavonols (flavonol-MUTAB-AuNPs) were designed. Free radical scavenging and antibacterial experiments show that flavonol-MUTAB-AuNPs greatly improve the scavenging effect on DPPH, hydroxyl and superoxide anion radicals, and significantly enhance the inhibition effect on Staphylococcus aureus and Escherichia coli compared with flavonols and AuNPs. Then γ-globulin, fibrinogen, trypsin and pepsin were selected as representative proteins and their interaction with flavonol-MUTAB-AuNPs were investigated by various spectroscopic techniques. The fluorescence quenching mechanism of these four proteins by flavonol-MUTAB-AuNPs is static quenching. The binding constants K a between them are in the range of 10 3 to 10 6 . The interaction between them is endothermic, entropy-driven spontaneous process, and the main non-covalent force is the hydrophobic interaction. The effect of flavonol-MUTAB-AuNPs on the structure of the four proteins were investigated using UV-vis absorption spectra, synchronous fluorescence spectra and circular dichroism spectra. These results offer important insights into the essence of the interaction between flavonol-MUTAB-AuNPs and γ-globulin/fibrinogen/trypsin/pepsin. They will contribute to the development of safe and effective flavonol-MUTAB-AuNPs in biomedical fields., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The objective of this study was to optimize the separation and purification of dihydromyricetin (DMY) from vine tea to obtain high purity, antibacterial and antioxidant crystal forms. We developed a cocrystallization approach for separation of DMY from vine tea with easy operation and high efficiency. The type and concentration of co-formers as well as solvent for separation have been investigated in detail. Under the optimal conditions, DMY with a purity of 92.41% and its two co-crystal forms (purity >97%) can be obtained. Three DMY crystal forms had consistent and good antioxidant activities according to DPPH radical scavenging results. DMY had effective antibacterial activity against the two kinds of drug-resistant bacteria including CRAB and MRSA, and DMY co-crystals had a greater advantage than DMY itself on CRAB. This work implies that cocrystallization can be used for the DMY separation and enhanced its anti-drug-resistant bacteria activity in food preservation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The quercetin dioxygenases (QDOs) are unusual metalloenzymes in that they display ring-opening dioxygenase activity with several different first-row transition metal ions which do not undergo redox changes during turnover. The QDOs are also unique in that the substrate binds as an η 1 -flavonolate rather than the η 2 - bidentate mode seen in all reported model complexes. The flavonol substrates were early examples of excited state intramolecular proton transfer (ESIPT) phenomena, in which photoexcitation causes an H-atom exchange between the adjacent hydroxyl and ketone, generating an oxidopyrylium emissive state. These oxidopyryliums undergo ring-opening dioxygenations analogous to the enzymatic reactions. Our hypothesis is that lability of the divalent metal ion may allow access to a reactive oxidopyrylium intermediate via coordination switching from the oxy to ketone position, which allows reaction with O 2 . In this report, we use a straight-forward methylation strategy to generate a panel of flavonol and thioflavonol derivatives modeling several η 1 - and η 2- coordination modes. Methylation of 3-hydroxythioflavone generates an air stable η 1 hydroxopyrylium salt, which undergoes rapid ring-opening dioxygenation by deprotonation or photoexcitation. By comparison, the η 1 -methoxyflavonol does not react with O 2 under any condition. We find that any of the studied flavonol derivatives, η 1 or η 2 , which demonstrates ESIPT-like oxidopyrylium emissions undergo QDO-like ring-opening reactions with dioxygen. The implications of these results concerning the mechanism of QDOs and related dioxygenases is discussed., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Patrick Farmer reports financial support and equipment, drugs, or supplies were provided by Baylor University., (Copyright © 2023 Elsevier Inc. All rights reserved.)

This study was to compare GABase [a mixture of γ -aminobutyric acid (GABA) aminotransferase and succinic semialdehyde dehydrogenase] and glutaminase inhibitory activities of 20 herbal extracts and investigate the isolation, structural elucidation and those inhibitory activities of three acylated flavonol monoglycosides from the selected extract of Laurus nobilis L. (laurel). On the basis of the NMR spectroscopic data and the ESI MS spectra together with the comparison with the literature values, three compounds were identified as kaempferol-3- O -(4″- E - p -coumaroyl)- α -l-rhamnopyranoside ( 1 ), kaempferol-3- O -(3″,4″-di- E - p -coumaroyl)- α -l-rhamnopyranoside ( 2 ) and kaempferol-3- O -(2″,4″-di- E - p -coumaroyl)- α -l-rhamnopyranoside ( 3 ), respectively. The IC 50 values of GABase inhibitory activity of 1-3 and p -hydroxybenzaldehyde (HBA) as control were 0.24 mM, 0.14 mM, 0.12 mM and 0.43 mM, respectively. Additionally, the IC 50 values of glutaminase inhibitory activity of 1-3 and 6-diazo-5-oxo-l-norleucine (DON) as control were 0.34 mM, 0.13 mM, 0.14 mM and 0.33 mM, respectively. The results suggest that the extract from laurel shows the strongest biological activities among 20 herbal extracts and three acylated flavonol monoglycosides may serve as potential lead compounds for the prevention and treatment of neurodegenerative and lifestyle-related diseases by targeting GABase and glutaminase. This is the first report on GABase and glutaminase inhibitory activities of 1-3 ., (© 2023 Walter de Gruyter GmbH, Berlin/Boston.)

The structure-activity relationship and inhibitory mechanism of flavonols on α-glucosidase were studied by inhibition kinetics, multispectral study, and molecular docking. The flavonols of rutin, quercetin and kaempferol effectively inhibit the activity of α-glucosidase, among which quercetin and rutin showed the strongest and weakest inhibitory abilities, respectively. The inhibitory ability of flavonols was enhanced by hydroxylation at C3' of B ring, while it was weakened by diglycosylation at C3 of C ring. Remarkably, the quenching affinity and inhibitory ability of flavonols were inconsistent, which was different from the conclusions reported by some previous studies. This may be ascribed to the hydroxyl groups of C3' of B ring and C3 of C ring. Furthermore, three flavonols were spontaneously bound to α-glucosidase through hydrophobic interactions and hydrogen bonding, which caused the structure and hydrophobic microenvironment of α-glucosidase to change, resulting in significant inhibition of α-glucosidase by flavonols., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Six new flavonols, including four glucosylated flavonols (dysosmaflavonoid A-D), one phenylpropanoid-substituted flavonol (dysosmaflavonoid E), and one phenyl-substituted flavonol (dysosmaflavonoid F), together with five known analogues, were isolated from the roots and rhizomes of Dysosma versipellis. Their structures were elucidated by comprehensive analysis of their NMR, IR, UV, HRESIMS, and HPLC data. The antioxidant activities of all isolated compounds were examined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Compounds 2, 3, 5-8, and 12 exhibited significant DPPH scavenging capacity with IC 50 values of 33.95, 39.02, 31.17, 32.79, 31.85, 30.48, and 23.75 μM, respectively, in comparison with Trolox (IC 50 , 15.80 μM). Compound 12 displayed more potent DPPH radical scavenging activity than prenylated and (or) glucosided derivatives (2-4, or 10). The preliminary structure-activity relationship showed that the catechol structure in flavonol is essential for DPPH radical scavenging effect., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest., (Copyright © 2023. Published by Elsevier B.V.)

Background: Pruned vine shoots prepared as toasted fragments (SEGs) have recently been proposed as enological additives capable of producing differentiated quality wines. In this work, the composition of phenolic and volatile compounds of SEGs, before and after contact with wines, has been studied., Results: SEGs from Tempranillo and Cabernet Sauvignon were used, which were kept in contact for 30 days with red wines made with the same varieties. Phenolic compounds were the ones with the highest sorption in SEGs, but a variety-dependent behavior was observed in anthocyanins and flavonols, with an increase in some malvidin derivatives only in Tempranillo wine and an increase in (-)-epicatechin in SEGs and Cabernet Sauvignon wine. trans-Resveratrol was transferred from SEGs to wine but also increased in SEGs regardless of the variety used. The volatile compounds that were most retained in SEGs were phenylethyl alcohol and ethyl lactate, but in lower proportions than the phenolic compounds and without important changes in wines., Conclusion: The high content of phenolic compounds in SEGs after their use as enological additives suggests that they could be considered as a source of anthocyanins and as raw materials for phenolic compounds with recognized antioxidant properties. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

Anthocyanidins, leucoanthocyanidins, and flavonols are natural compounds mainly known due to their reported biological activities, such as antiviral, antifungal, anti-inflammatory activities, and antioxidant activity. In the present study, we performed a comparative structural, conformational, electronic, and nuclear magnetic resonance analysis of the reactivity of the chemical structure of primary anthocyanidins, leucoanthocyanidins, and flavonoids. We focused our analysis on the following molecular questions: (i) differences in cyanidin catechols ( +)-catechin, leucocyanidin, and quercetin; (ii) the loss of hydroxyl presents in the R1 radical of leucoanthocyanidin in the functional groups linked to C4 (ring C); and (iii) the electron affinity of the 3-hydroxyl group (R7) in the flavonoids delphinidin, pelargonidin, cyanidin, quercetin, and kaempferol. We show unprecedented results for bond critical point (BCP) of leucopelargonidin and leucodelphirinidin. The BCP formed between hydroxyl hydrogen (R2) and ketone oxygen (R1) of kaempferol has the same degrees of covalence of quercetin. Kaempferol and quercetin exhibited localized electron densities between hydroxyl hydrogen (R2) and ketone oxygen (R1). Global molecular descriptors showed quercetin and leucocyanidin are the most reactive flavonoids in electrophilic reactions. Complementary, anthocyanidins are the most reactive in nucleophilic reactions, while the smallest gap occurs in delphinidin. Local descriptors indicate that anthocyanidins and flavonols are more prone to electrophilic attacks, while in leucoanthocyanidins, the most susceptible to attack are localized in the ring A. The ring C of anthocyanidins is more aromatic than the same found in flavonols and leucoanthocyanidins. METHODS: For the analysis of the molecular properties, we used the DFT to evaluate the formation of the covalent bonds and intermolecular forces. CAM-B3LYP functional with the def2TZV basis set was used for the geometry optimization. A broad analysis of quantum properties was performed using the assessment of the molecular electrostatic potential surface, electron localization function, Fukui functions, descriptors constructed from frontier orbitals, and nucleus independent chemical shift., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Transferrin is the indispensable component in the body fluids and has been explored as a potential drug carrier for target drugs to cancer cells. Flavonols are widely distributed in plants and shown a wide range of biological activities. In the present study, the interaction between flavonols (including galangin, kaempferol, quercetin, and myricetin) and transferrin under physiological conditions was investigated by using experimental as well as computational approaches. Fluorescence data reveal that the fluorescence quenching mechanism of transferrin by flavonols is static quenching. Transferrin has moderate affinity with flavonols, and the binding constants (K a ) are 10 3 -10 4 L/mol. In addition, there are two different binding sites for the interaction between kaempferol and transferrin. Thermodynamic parameter analysis shows that the interaction of flavonols and transferrin is synergistically driven by enthalpy and entropy. Hydrophobic interaction, electrostatic force and hydrogen bonds are the main force types. Synchronous fluorescence spectroscopy shows that flavonols decrease the hydrophobicity of the microenvironment around tryptophan (Trp) and have no effect on the microenvironment around tyrosine (Tyr). UV-vis and CD spectra show that the interaction between transferrin and flavonols leads to the loosening and unfolding of transferrin backbone. The increase of β-sheet is accompanied by the decrease of α-helix and β-turn. The specific binding sites of flavonols to transferrin are confirmed by molecular docking. Molecular dynamic simulation suggests that the transferrin-flavonols docked complex is stable throughout the simulation trajectory., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Hibiscus rosa-sinensis plants are mainly cultivated as ornamental plants, but they also have food and medicinal uses. In this work, 16 H. rosa-sinensis cultivars were studied to measure their colorimetric parameters and the chemical composition of hydroethanolic extracts obtained from their petals. These extracts were characterized using UHPLC-ESI + -Obitrap-MS, and their antioxidant activity was evaluated using the ORAC assay. The identified flavonoids included anthocyanins derived from cyanidin, glycosylated flavonols derived from quercetin and kaempferol, and flavan-3-ols such as catechin and epicatechin. Cyanidin-sophoroside was the anthocyanin present in extracts of lilac, pink, orange, and red flowers, but was not detected in extracts of white or yellow flowers. The total flavonol concentration in the flower extracts was inversely proportional to the total anthocyanin content. The flavonol concentration varied according to the cultivar in the following order: red < pink < orange < yellow ≈ white, with the extract from the red flower presenting the lowest flavonol concentration and the highest anthocyanin concentration. The antioxidant activity increased in proportion to the anthocyanin concentration, from 1580 µmol Trolox ® /g sample (white cultivar) to 3840 µmol Trolox ® /g sample (red cultivar).

Nature exploits transition metal centers to enhance and tune the oxidizing power of natural oxidants such as O 2 and H 2 O 2 . The design and interrogation of synthetic metallocomplexes with similar reactivity to metalloproteins provides one strategy for gaining insight into the mechanistic underpinnings of oxygen-activating enzymes such as oxidases, oxygenases, and dioxygenases like Ni-quercetinase (Ni-QueD). Ni-QueD catalyzes the oxidative ring opening of the polyphenol quercetin, a natural product with antioxidant properties. Herein, we report the synthesis and characterization of Ni(13-DOB), a Ni(II) species complexed by an N4-macrocycle that has been characterized by single crystal X-ray crystallography. Ni(13-DOB) forms a Ni-superoxide intermediate (Ni(13-DOB)O 2 •- ) upon treatment with H 2 O 2 and Et 3 N, as verified by resonance Raman spectroscopy. We demonstrate through UV/vis and LCMS that Ni(13-DOB)O 2 •- is capable of the 1-electron oxidation of flavonols, including both 3-hydroxyflavone (3-HF, the simplest flavonol) and quercetin itself. Incorporation of two O-atoms into the flavonol radical via superoxide from Ni(13-DOB)O 2 •- precedes oxidative cleavage of the flavonol scaffold in each case, consistent with quercetinase ring cleavage by Ni-QueD in Streptomyces sp. FLA. Conversion of 3-HF into 2-hydroxybenzoylbenzoic acid was accomplished with catalytic turnover of Ni(13-DOB) at ambient temperature, as confirmed by HPLC timecourses and GCMS analysis of isotopic labeling studies. The Ni(13-DOB)-mediated oxidative cleavage of quercetin to the corresponding biomimetic phenolic ester was also verified through 18 O-isotopic labeling studies. Through the HPLC characterization of both on- and off-pathway products of flavonol dioxygenation by Ni(13-DOB)O 2 •- , the stringent reaction pathway control provided by enzyme active sites is highlighted., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

Background: Phytochemicals belonging to the class of flavonoids have been used in medicine for the treatment of different kinds of human health complications. Flavonoids have beneficial health aspects in medicine mainly due to their anti-microbial, anti-diabetic, anti-inflammatory, anticancer, and anti-carcinogenic activities. They have been scientifically investigated for their health benefit and pharmacological activities in medicine. Engeletin is a pure flavanonol class phytocompound present in the skin of white grapes and white wine. Engeletin has numerous pharmacological activities in medicine., Methods: In order to know the beneficial health aspects of engeletin in medicine, scientific data on engeletin have been collected from different literature sources and analyzed in the present work. The present work summarized the important findings of engeletin with respect to its medicinal uses, pharmacological activities, and analytical aspects in medicine. All the scientific data were collected from PubMed, Google, Scopus, Science Direct and Google Scholar and analyzed in the present work., Results: Scientific data analysis of research works revealed the biological importance and therapeutic benefit of engeletin in medicine. Engeletin has attracted scientific attention mainly due to its antiinflammatory and anti-tumor potential. Engeletin could inhibit the occurrence of cervical cancer and delay the development of liver damage and lung cancer in mice. Engeletin was found to inhibit lipopolysaccharides- induced endometritis in mice by inhibiting the inflammatory response. Pharmacological data analysis revealed the therapeutic importance of engeletin against acute lung injury, inflammatory diseases, liver injury, pulmonary fibrogenesis, Alzheimer's disease, endometritis, cervical carcinogenesis, lung cancer, and osteoarthritis. Analytical data signified the importance of modern analytical tools for separating, isolating, and identifying engeletin., Conclusion: Scientific data analysis revealed the biological importance and therapeutic benefit of engeletin in medicine and other allied health sectors., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Prenylated flavonol glycosides in Epimedium plants, as key medicinal components, are known to have great pharmaceutical activities for human health. Among the main prenylated flavonol glycosides, the modification mechanism of different sugar moieties is still not well understood. In the current study, a novel prenylated flavonol rhamnoside xylosyltransferase gene ( EpF3R2″XylT ) was cloned from E. pubescens , and the enzymatic activity of its decoding proteins was examined in vitro with different prenylated flavonol rhamnoside substrates and different 3- O -monosaccharide moieties. Furthermore, the functional and structural domains of EpF3R2″XylT were analyzed by bioinformatic approaches and 3-D protein structure remodeling. In summary, EpF3R2″XylT was shown to cluster with GGT (glycosyltransferase that glycosylates sugar moieties of glycosides) through phylogenetic analysis. In enzymatic analysis, EpF3R2″XylT was proven to transfer xylose moiety from UDP-xylose to prenylated flavonol rhamnoside at the 2″-OH position of rhamnose. The analysis of enzymatic kinetics showed that EpF3R2″XylT had the highest substrate affinity toward icariin with the lowest K m value of 75.96 ± 11.91 mM. Transient expression of EpF3R2″XylT in tobacco leaf showed functional production of EpF3R2″XylT proteins in planta. EpF3R2″XylT was preferably expressed in the leaves of E. pubescens , which is consistent with the accumulation levels of major prenylflavonol 3- O -triglycoside. The discovery of EpF3R2″XylT will provide an economical and efficient alternative way to produce prenylated flavonol trisaccharides through the biosynthetic approach.

Mono- and poly- O -methylated flavonols and their glycoside derivatives belong to the group of natural plant polyphenols with a wide spectrum of pharmacological activities. These compounds are known for their antioxidant, antimutagenic, hepatoprotective, antidiabetic, and antilipogenic properties. Additionally, they inhibit carcinogenesis and cancer development. Having in mind the multidirectional biological activity of methylated flavonols, we would like to support further study on their health-promoting activities; in this review we summarized the most recent reports on syringetin and some of its structural analogues: laricitrin, ayanin, and isorhamnetin. Natural sources and biological potential of these substances were described based on the latest research papers.

Phenolic plant constituents are well known for their health-promoting and cancer chemopreventive properties, and products containing such constituents are therefore readily consumed. In the present work, we isolated 13 phenolic constituents of four different compound classes from the aerial parts of the Moldavian dragonhead, an aromatic and medicinal plant with a high diversity on secondary metabolites. All compounds were tested for their apoptotic effect on myeloma (KMS-12-PE) and AML (Molm-13) cells, with the highest activity observed for the flavone and flavonol derivatives. While diosmetin ( 6 ) exhibited the most pronounced effects on the myeloma cell line, two polymethylated flavones, namely cirsimaritin ( 1 ) and xanthomicrol ( 3 ), were particularly active against AML cells and therefore subsequently investigated for their antiproliferative effects at lower concentrations. At a concentration of 2.5 µM, cirsimaritin ( 1 ) reduced proliferation of Molm-13 cells by 72% while xanthomicrol ( 3 ) even inhibited proliferation to the extent of 84% of control. In addition, both compounds were identified as potent FLT3 inhibitors and thus display promising lead structures for further drug development. Moreover, our results confirmed the chemopreventive properties of flavonoids in general, and in particular of polymethylated flavones, which have been intensively investigated especially over the last decade.

This paper demonstrates the metal ion effects on the quercetin 2,4-dioxygenase (2,4-QD)-like reactivity. For this purpose, a series of five metal(II)-acetato complexes [M II (L)(OAc)] {M = Mn (1OAc), Co (2OAc), Ni (3OAc), Cu (4OAc), Zn (5OAc); OAc = acetate} supported with a newly designed N 3 O-donor carboxylato ligand L - {L - = 2-((benzyl((6'-methyl-[2,2'-bipyridin]-6-yl)methyl)amino)methyl)benzoate} has been synthesised as models for the active sites of M II -substituted 2,4-QDs. The enzyme-substrate (ES) model complexes [M II (L)(fla)] {M = Mn (1fla), Co (2fla), Ni (3fla), Cu (4fla), Zn (5fla); flaH = flavonol} have been synthesised by reacting flaH with their corresponding acetate-bound complexes in basic conditions. Detailed physicochemical properties of all the compounds are reported. Furthermore, single-crystal X-ray diffractions have been done to determine the structures of the compounds 2OAc·2H2O, 3OAc, 4OAc·CH2Cl2·2H2O, 5OAc·2H2O and 2fla·MeOH. The enzymatic reactivities of complexes 1OAc-5OAc towards the dioxygenation of flavonol have been explored in detail. All the complexes effectively catalyse the oxygenative degradation of flavonol in N , N -dimethylformamide (DMF) medium at 70 °C under multiple-turnover conditions and produce enzyme-type products. Kinetic investigations were performed to see the metal ions' effects on reactivity. The reaction rates vary with the metal ions, showing the order Co > Ni > Zn > Mn > Cu. The studies reveal that the reactivities of the [M II (L)(OAc)] complexes are governed primarily by three factors viz the ES adduct formation constant ( K f ), the redox potential ( E pa ) of the bound fla - /fla˙ couple, and the degree of delocalisation of the fla˙ radical with the metal electrons, which are drastically influenced by the M 2+ ions. In the mechanistic interpretation, a single-electron transfer (SET) from the bound-flavonolate to dioxygen has been proposed to generate the catalytically important "M(II)-fla˙" radical and superoxide ion, which react further to bring about the dioxygenation reaction. The identification of the metal(II)-bound flavonoxy radical intermediate for the case of cobalt using EPR spectroscopy and the detection of superoxide ion by NBT 2+ test and EPR spin-trapping experiment (DMPO test) are remarkable in envisaging the reaction pathway.

Flavonols are found in plants as aglycones and as glycosides. Antioxidant activity of flavonols may occur via several mechanisms within the cell, and mitochondria as a target may play an important role. There is a lack of information about the influence of the sugar moiety on biological activity of flavonoid glycosides. The aims of study were to investigate the effects of quercetin and its glycosides on mitochondrial respiration rates at various metabolic states, and to evaluate their antioxidant potential using chemical and biological approaches. Mitochondrial function was measured using an oxygraphic method, cytochrome c reduction spectrophotometrically, H 2 O 2 generation in mitochondria fluorimetrically, and antioxidant activity of flavonoids using an HPLC-post column system. Our data revealed that quercetin and its glycosides isoquercitrin, rutin, and hyperoside uncouple kidney mitochondrial respiration (increasing the State 2 respiration rate) and significantly reduce cytochrome c. Moreover, quercetin, and its glycosides decrease the production of mitochondrial H 2 O 2 and possess radical scavenging and ferric reducing capacities. The highest activity was characteristic for quercetin, showing that the sugar moiety significantly diminishes its activity. In conclusion, our results show the efficient radical scavenging, ferric and cytochrome c reducing capacities, and uncoupling properties of quercetin and its glycosides, as well as the importance of the sugar residue and its structure in the regulation of kidney mitochondrial function.

Five undescribed fatty acid esters of flavonol glycosides, nephelosides A-E, along with eight known compounds, were isolated from the seeds of Nephelium lappaceum L. The structures were elucidated by extensive analysis of spectroscopic data in combination with GC-MS analysis. Potency of compounds toward nitric oxide suppression was assessed by monitoring the inhibition of lipopolysaccharide-stimulated nitric oxide production in J744.A1 macrophage cells. Nepheloside D, kaempferol and kaempferol 7-O-α-L-rhamnopyranoside showed significant activity with IC 50 values of 26.5, 11.6 and 12.0 μM, respectively., (Copyright © 2022. Published by Elsevier Ltd.)

Most previous studies have been focused on isoflavone profile with biological activities from soybean seed and its related products. However, in the present study, eighty-three flavonoid derivatives (55 flavonols, 9 flavones and 19 isoflavones) were comprehensively identified and quantified from young leaves of 21 core-collected soybean cultivars based on ultra-performance liquid chromatography-diode array detector with quadrupole time of flight/mass spectrometry (UPLC-DAD-QToF/MS). Among total flavonoids from soybean leaves (SLs), the abundant flavonols (83.6%) were primarily composed of di- and tri- glycosides combined to the aglycones (K, kaempferol; Q, quercetin; I, isorhamnetin). Particularly, K-rich SLs (yellow coated seed), Nongrim 51 (breeding line) and YJ208-1 (landrace) contained mainly kaempferol 3-O-(2″-O-glucosyl-6″-O-rhamnosyl)galactoside and 3-O-(2″,6″-di-O-rhamnosyl)galactoside, and were expected to be superior cultivars by their higher flavonoids. Besides, the new tri-I-glycosides (soyanins I-V) were presented as predominant components in Junyeorikong (landrace, black). Thus, this study suggest that the SLs can be considered as valuable edible resources due to their rich flavonoids. Also, these detailed profiles will support breeding of superior varieties with excellent biological activities as well as relationship with seed anthocyanins production, and contribute to perform metabolomics approach to investigate the changes of SLs flavonols during the leaf growth and fermentation in further research., (© 2022. The Author(s).)

Background: Enzymatic catalyzed grafting of oligosaccharides with polyphenols is a safe and environmentally friendly approach to simultaneously enhance the bioactivity of oligosaccharides and the solubility of polyphenols. In this study, chitosan oligosaccharide (COS) was grafted with three different flavonols including myricetin (MYR), quercetin (QUE) and kaempferol (KAE) by horseradish peroxidase (HRP) catalysis. The structures, antioxidant activity and edible coating application of COS-flavonol conjugates were investigated., Results: The total phenol content of COS-MYR, COS-QUE and COS-KAE conjugates was 59.89, 68.37 and 53.77 mg gallic acid equivalents g -1 , respectively. Thin layer chromatography showed the conjugates did not contain ungrafted flavonols. COS-flavonol conjugates showed ultraviolet absorption peak at about 294 nm, corresponding to the A-ring of flavonols. Fourier-transform infrared spectra of conjugates confirmed the formation of Schiff-base and Michael-addition products. The proton-nuclear magnetic resonance spectrum of COS-KAE conjugate exhibited phenyl proton signals of KAE. X-ray diffraction patterns of conjugates showed some diffraction peaks of flavonols. COS-flavonol conjugates presented rough and porous morphologies with sheet-like and/or blocky structures. The conjugates showed higher water solubility, free radical scavenging activity and reducing power than flavonols. Moreover, fish gelatin/COS-flavonol conjugate coatings effectively prolonged the shelf life of refrigerated largemouth bass (Micropterus salmoides) fillets from 5 days to 7-8 days., Conclusion: COS-flavonol conjugates prepared by HRP catalysis have great potentials as novel antioxidant agents. © 2022 Society of Chemical Industry., (© 2022 Society of Chemical Industry.)

Two new flavonol glycosides 3,5,7-trimethoxyflavone-4'-O-[5'''-O- p -coumaroyl- β -D-apiofuranoyl-(1'''→2'')- β -D-glucopyranoside] ( 1 ) and 3,5,7-trimethoxyflavone -4'-O- β -D-glucopyranoside ( 2 ) were isolated from Selaginella tamariscina . The structures of 1 and 2 were elucidated on the basis of chemical and spectral analysis, including 1D, 2D NMR analyses and HRESIMS spectrometry. Two compounds were evaluated for cytotoxic activities against A-375, MCF-7, MDA-MB-231 and MDA-MB-468 cell lines by MTT assay. Unfortunately, two compounds displayed no cytotoxic activities.

Flavonols have been studied extensively because of their interesting biological activities and excited-state intramolecular proton transfer (ESIPT) behavior. Galangin, kaempferol, quercetin, and myricetin are structurally related flavonols that differ only in the number of B-ring hydroxyl substituents. In this work, we have carried out a detailed study on the photophysical behavior of these structurally related flavonols in various solvents and a 1,2-dimyristoyl- sn -glycero-3-phosphocholine (DMPC) small unilamellar vesicles (SUVs) model membrane. We observed that these flavonols exist in different forms in the ground and excited states depending on the nature of the solvent. The weak intrinsic fluorescence of these flavonols gets enhanced in hydrogen-bond-accepting and alcoholic solvents. The phototautomer fluorescence intensity of these flavonols increases significantly in the DMPC membrane compared to water, suggesting ESIPT activation via binding interaction between flavonols and the membrane. According to our findings, both the number of B-ring hydroxy groups and membrane fluidity affect the flavonol binding with the membrane. The steady-state fluorescence intensity, steady-state anisotropy, fluorescence lifetime, and fluorescence anisotropy decay of flavonols were sensitive towards the temperature-induced DMPC membrane phase change. A quenching study has been performed to investigate the location and distribution of flavonols in the DMPC SUVs. Moreover, the antioxidant potential of flavonols in DMPC SUVs has been examined using the DPPH scavenging method. Our results reveal that the B-ring hydroxy groups significantly affect the photophysics, binding affinity, location, distribution, and DPPH scavenging activity of polyhydroxy-flavonols in the DMPC SUVs.

Oxidative stress that damages cellular components affects various organs including the brain. It is thus believed to play an active role in neurodegenerative diseases, wherein the intrinsic antioxidant enzymes metabolize toxic intermediates. For therapeutic purpose, instead of antioxidant enzymes, small organic compounds as antioxidants may be more effective. Here, reducing power and electrochemical behavior of some flavanols, flavanonols, flavones, flavonols and O-methylated flavonols have been estimated and confirmed by the calculated bond dissociation energy. Compared to other classes, flavonols exhibited increased reducing power that decreased with methylation of the oxygen atom in the B-ring. Gossypetin emerged as the most effective of these flavonols. Generally, compounds with two hydroxyl groups in two consecutive positions of the phenyl ring and an enolic group in the C-ring with more preference for the hydroxyl group in the ortho position with respect to each other in the catechol moiety showed major activity. 5 position of the A-ring showed the least effect on the activity. The present understanding therefore may be applied for identifying compounds to be used as scaffold for designing potent antioxidants., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Flaxseed and soybean are an important source of lignans and flavonoids. Previously, the metabolism of isoflavones and lignans from soybean and flaxseed extracts by the microbiota of adult individuals (n = 14) and infants (n = 23) was analyzed. Thus, the present study aimed to examine the metabolism of flavones, flavanones and flavonols, as well as the production of phenolic acids, by the intestinal microbiota of these individuals., Results: Concentrations of aglycones of flavonoids, such as herbacetin, quercetin, quercetagetin, myricetin, kaempferol, apigenin and luteolin, increased for most of individuals as a consequence of deglycosylation reactions. On the other hand, a diminution in the antioxidant activity and phenolic compound concentration and an increase in the concentration of 3,4-dihydroxyphenylacetic acid, 2-(4-hydroxyphenyl)-propionic acid, protocatechuic acid and catechol was also observed., Conclusion: The present study found that deglycosylation reactions were the main reactions and accelerated the formation of more bioavailable flavonoids, with greater biological activity, in most of the individuals. However, other reactions also occurred, including the total or partial catabolism of flavonoids. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)

Four copper(II)-flavonolate compounds of type [Cu(L R )(fla)] {where L R = 2-( p -R-benzyl(dipyridin-2-ylmethyl)amino)acetate; R = -OMe (1), -H (2), -Cl (3) and -NO 2 (4)} have been developed as a structural and functional enzyme-substrate (ES) model of the Cu 2+ -containing quercetin 2,4-dioxygenase enzyme. The ES model complexes 1-4 are synthesized by reacting 3-hydroxyflavone in the presence of a base with the respective acetate-bound copper(II) complexes, [Cu(L R )(OAc)]. In the presence of dioxygen the ES model complexes undergo enzyme-type oxygenolysis of flavonolate (dioxygenase type bond cleavage reaction) at 80 °C in DMF. The reactivity shows a substituent group dependent order as -OMe (1) > -H (2) > -Cl (3) > -NO 2 (4). Experimental and theoretical studies suggest a single-electron transfer (SET) from flavonolate to dioxygen, rather than valence tautomerism {[Cu II (fla - )] ↔ [Cu I (fla˙)]}, to generate the reactive flavonoxy radical (fla˙) that reacts further with the superoxide radical to bring about the oxygenative ring opening reaction. The SET pathway has been further verified by studying the dioxygenation reaction with a redox-inactive Zn 2+ complex, [Zn(L OMe )(fla)] (5).

Natural flavonoids, in addition to some of their synthetic derivatives, are recognized for their remarkable medicinal properties. The present study was designed to investigate the in vitro antioxidant and in vivo antistress effect of synthetic flavonoids (flavones and flavonols) in mice, where stress was induced by injecting acetic acid and physically through swimming immobilization. Among the synthesized flavones ( F1-F6 ) and flavonols ( OF1-OF6 ), the mono para substituted methoxy containing F3 and OF3 exhibited maximum scavenging potential against DPPH (2,2-diphenyl-1-picrylhydrazyl) with IC 50 of 31.46 ± 1.46 μg/mL and 25.54 ± 1.21 μg/mL, respectively. Minimum antioxidant potential was observed for F6 and OF6 with IC 50 values of 174.24 ± 2.71 μg/mL and 122.33 ± 1.98 μg/mL, respectively, in comparison with tocopherol. The ABTS scavenging activity of all the synthesized flavones and flavonols were significantly higher than observed with DPPH assay, indicating their potency as good antioxidants and the effectiveness of ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) assay in evaluating antioxidant potentials of chemical substances. The flavonoids-treated animals showed a significant (* p < 0.05, ** p < 0.01 and *** p < 0.001, n = 8) reduction in the number of writhes and an increase in swimming endurance time. Stressful conditions changed plasma glucose, cholesterol and triglyceride levels, which were used as markers when evaluating stress in animal models. The level of these markers was nearly brought to normal when pre-treated with flavones and flavonols (10 mg/kg) for fifteen days in experimental animals. These compounds also considerably reduced the levels of lipid peroxidation (TBARS: Thiobarbituric acid reactive substances), which was significant (* p < 0.05, ** p < 0.01 and *** p < 0.001, n = 8) compared to the control group. A significant rise in the level of catalase and SOD (super oxide dismutase) was also observed in the treated groups. Diazepam (2 mg/kg) was used as the standard drug. Additionally, the flavonoids markedly altered the weight of the adrenal glands, spleen and brain in stress-induced mice. The findings of the study suggest that these flavonoids could be used as a remedy for stress and are capable of ameliorating diverse physiological and biochemical alterations associated with stressful conditions. However, further experiments are needed to confirm the observed potentials in other animal models, especially in those with a closer resemblance to humans. Toxicological evaluations are also equally important.

Obesity is becoming increasingly common all over the world and global strategies are accordingly being developed to prevent it. In order to support the strategies, the effects of green apple (Golden Delicious) and the consumption of its three major flavonols (quercetin-3-glucoside, quercetin-3-D-galactoside, and quercetin-3-rhamnoside) on body weight; the weight of liver, kidney, and spleen; some lipid parameters in serum; and total lipid ratios of liver and kidney and oxidative stress parameters of obese rats were studied. This study was conducted on two experimental groups: one of which was given an apple, and the other was given flavonols, in addition to their high-energy diet; along with a sham and a control rat group, for 4 weeks. According to results, there was no difference in body and organ weights between groups. The liver and kidney weights increased in obese rats, but there was no difference between the total lipid ratios in these organs. The addition of green apple and selected flavonols to the high-energy diet of rats was not sufficient to prevent the increase in body and organ weights, but it supported the reduction in some lipid fractions and in oxidative stress parameters of obese rats. Moreover, this study supported the argument that obesity causes most of the lipid fractions increase in serum and induces oxidative stress.

Single-stranded DNA (ssDNA)-binding protein (SSB) plays a crucial role in DNA replication, repair, and recombination as well as replication fork restarts. SSB is essential for cell survival and, thus, is an attractive target for potential antipathogen chemotherapy. Whether naturally occurring products can inhibit SSB remains unknown. In this study, the effect of the flavonols myricetin, quercetin, kaempferol, and galangin on the inhibition of Pseudomonas aeruginosa SSB (PaSSB) was investigated. Furthermore, SSB was identified as a novel quercetin-binding protein. Through an electrophoretic mobility shift analysis, myricetin could inhibit the ssDNA binding activity of PaSSB with an IC 50 of 2.8 ± 0.4 μM. The effect of quercetin, kaempferol, and galangin was insignificant. To elucidate the flavonol inhibition specificity, the crystal structure of PaSSB complexed with the non-inhibitor quercetin was solved using the molecular replacement method at a resolution of 2.3 Å (PDB entry 7VUM) and compared with a structure with the inhibitor myricetin (PDB entry 5YUN). Although myricetin and quercetin bound PaSSB at a similar site, their binding poses were different. Compared with myricetin, the aromatic ring of quercetin shifted by a distance of 4.9 Å and an angle of 31 o for hydrogen bonding to the side chain of Asn108 in PaSSB. In addition, myricetin occupied and interacted with the ssDNA binding sites Lys7 and Glu80 in PaSSB whereas quercetin did not. This result might explain why myricetin could, but quercetin could not, strongly inhibit PaSSB. This molecular evidence reveals the flavonol inhibition specificity and also extends the interactomes of the natural anticancer products myricetin and quercetin to include the OB-fold protein SSB.

Fifteen metabolites, including two flavonols (1-2), three lignans (3-5), and ten diterpenoids (6-15), were isolated from the leaves of Pinus yunnanensis. Among them, flavanonol (1) were identified as undescribed flavonol derivative with natural rarely B-ring fission lactone. Massive spectroscopic methods, the DP4+ probabilities and CD/ECD calculations were applied to establish the structure of component 1. Among these compounds, taxifolin (2) showed potent cytotoxicity, having IC 50 values from 21.33 to 45.48 μg/mL, it also showed broad antibacterial activity against human pathogens with MIC values from 32 to 64 μg/mL., (© 2021 Wiley-VHCA AG, Zurich, Switzerland.)