5-Hydroxyflavone

7-Imidazolyl-substituted 4'-methoxy and 3',4'-dimethoxy-containing polyfluoroflavones as promising antiviral agents.[Pubmed:33071313]

J Fluor Chem. 2020 Dec;240:109657.

A simple and convenient method for the synthesis of new methyl 2-(4-methoxyphenyl)- and 2-(3,4-dimethoxyphenyl)-4-oxo-4H-polyfluorochromen-3-carboxylates as analogs of natural methoxy-containing flavones is proposed. As a result of their directed modification under basic conditions, 7-imidazolyl-substituted derivatives were obtained. In aqueous-organic medium under basic conditions, 5,6,7,8-tetrafluoro-3-(methoxycarbonyl)flavones were transformed into 6,8-difluoro-5-hydroxy-7-(1H-imidazol-1-yl)-3-(methoxycarbonyl)flavones as a result of flavone-5-Hydroxyflavone rearrangement, while 6,7,8-trifluorinated analogs underwent a flavone-coumarin rearrangement to give 6,8-difluoro-3-(hydroxyarylidene)-7-(1H-imidazol-1-yl)coumarins under the same conditions. Acid hydrolysis of methyl polyfluoroflavone-3-carboxylates allowed to obtain 2-aryl-4H-polyfluorochromen-4-ones. Evaluation of the antiviral activity of the synthesized compounds against influenza A (H1N1) and Coxsackie B3 viruses showed that 2-(3,4-dimethoxyphenyl)-5,6,8-trifluoro-7-(1H-imidazol-1-yl)-4H-chromene-4-one has the most promising properties.

Predictive QSAR model confirms flavonoids in Chinese medicine can activate voltage-gated calcium (CaV) channel in osteogenesis.[Pubmed:32256687]

Chin Med. 2020 Mar 31;15:31.

Background: Flavonoids in Chinese Medicine have been proven in animal studies that could aid in osteogenesis and bone formation. However, there is no consented mechanism for how these phytochemicals action on the bone-forming osteoblasts, and henceforth the prediction model of chemical screening for this specific biochemical function has not been established. The purpose of this study was to develop a novel selection and effective approach of flavonoids on the prediction of bone-forming ability via osteoblastic voltage-gated calcium (CaV) activation and inhibition using molecular modelling technique. Method: Quantitative structure-activity relationship (QSAR) in supervised maching-learning approach is applied in this study to predict the behavioral manifestations of flavonoids in the CaV channels, and developing statistical correlation between the biochemical features and the behavioral manifestations of 24 compounds (Training set: Kaempferol, Taxifolin, Daidzein, Morin, Scutellarein, Quercetin, Apigenin, Myricetin, Tamarixetin, Rutin, Genistein, 5,7,2'-Trihydroxyflavone, Baicalein, Luteolin, Galangin, Chrysin, Isorhamnetin, Naringin, 3-Methyl galangin, Resokaempferol; test set: 5-Hydroxyflavone, 3,6,4'-Trihydroxyflavone, 3,4'-Dihydroxyflavone and Naringenin). Based on statistical algorithm, QSAR provides a reasonable basis for establishing a predictive correlation model by a variety of molecular descriptors that are able to identify as well as analyse the biochemical features of flavonoids that engaged in activating or inhibiting the CaV channels for osteoblasts. Results: The model has shown these flavonoids have high activating effects on CaV channel for osteogenesis. In addition, scutellarein was ranked the highest among the screened flavonoids, and other lower ranked compounds, such as daidzein, quercetin, genistein and naringin, have shown the same descending order as previous animal studies. Conclusion: This predictive modelling study has confirmed and validated the biochemical activity of the flavonoids in the osteoblastic CaV activation.

Synthesis, Characterization, Cytotoxic Activity, and Metabolic Studies of Ruthenium(II) Polypyridyl Complexes Containing Flavonoid Ligands.[Pubmed:32191449]

Inorg Chem. 2020 Apr 6;59(7):4424-4434.

Four novel monocationic Ru(II) polypyridyl complexes were synthesized with the general formula [Ru(DIP)2flv]X, where DIP is 4,7-diphenyl-1,10-phenanthroline, flv stands for the flavonoid ligand (5-Hydroxyflavone in [Ru(DIP)2(5-OHF)](PF6), genistein in [Ru(DIP)2(gen)](PF6), chrysin in [Ru(DIP)2(chr)](OTf), and morin in [Ru(DIP)2(mor)](OTf)), and X is the counterion, PF6(-), and OTf (triflate, CF3SO3), respectively. Following the chemical characterization of the complexes by (1)H and (13)C NMR, mass spectrometry, and elemental analysis, their cytotoxicity was tested against several cancer cell lines. The most promising complex, [Ru(DIP)2(gen)](PF6), was further investigated for its biological activity. Metabolic studies revealed that this complex severely impaired mitochondrial respiration and glycolysis processes, contrary to its precursor, Ru(DIP)2Cl2, which showed a prominent effect only on the mitochondrial respiration. In addition, its preferential accumulation in MDA-MB-435S cells (a human melanoma cell line previously described as mammary gland/breast; derived from metastatic site: pleural effusion), which are used for the study of metastasis, explained the better activity in this cell line compared to MCF-7 (human, ductal carcinoma).

The Interaction of Flavonols with Membrane Components: Potential Effect on Antioxidant Activity.[Pubmed:31897501]

J Membr Biol. 2020 Feb;253(1):57-71.

Flavonols are the most widely distributed class of dietary flavonoids with a wide range of pharmacological properties due to their potent lipid peroxidation inhibition activity. The permeability and orientation of these compounds in lipid bilayers can provide an understanding of their antioxidant and lipid-peroxidation inhibition activity based on their structures at the molecular level. For this purpose, we studied antioxidant activity and atomic-scale molecular dynamics simulations of 3-hydroxyflavone (fisetin), 5-Hydroxyflavone (apigenin) and 3,5-Hydroxyflavone (morin) in palmitoyloleylphosphatidylcholine (POPC) membrane models with 0 mol% and 40 mol% cholesterol concentration. In pure POPC bilayer with 0 mol% cholesterol concentration, the flavonols penetrated into bilayer with lowest free energy profiles, however, incorporation of 40% cholesterol concentration reduced the permeability of the flavonols. Higher cholesterol concentrations in the POPC lipid bilayer resulted in an increase of the bilayer thickness and corresponding decrease in the area per lipid which rationalizes the reduced partitioning of flavonols due to cholesterol. In the presence of cholesterol, the flavonols reside at the polar interfacial region of the lipid bilayer to form higher H-bonding interactions with cholesterol molecules in addition to water and lipid oxygens. Among all the selected flavonols, morin showed the highest affinity which was driven by the hydrophobic effect as also depicted by ITC (Isothermal titration calorimetry) experiments and thus, more efficient antioxidant in scavenging superoxide, nitric oxide radicals as well as lipid peroxyl radicals. Furthermore, our simulations also confirmed that the permeability of compounds is sensitive towards the cholesterol content in the membrane.

Less Cytotoxic Protoflavones as Antiviral Agents: Protoapigenone 1'-O-isopropyl ether Shows Improved Selectivity Against the Epstein-Barr Virus Lytic Cycle.[Pubmed:31842358]

Int J Mol Sci. 2019 Dec 12;20(24). pii: ijms20246269.

Protoflavones, a rare group of natural flavonoids with a non-aromatic B-ring, are best known for their antitumor properties. The protoflavone B-ring is a versatile moiety that might be explored for various pharmacological purposes, but the common cytotoxicity of these compounds is a limitation to such efforts. Protoapigenone was previously found to be active against the lytic cycle of Epstein-Barr virus (EBV). Further, the 5-Hydroxyflavone moiety is a known pharmacophore against HIV-integrase. The aim of this work was to prepare a series of less cytotoxic protoflavone analogs and study their antiviral activity against HIV and EBV. Twenty-seven compounds, including 18 new derivatives, were prepared from apigenin through oxidative de-aromatization and subsequent continuous-flow hydrogenation, deuteration, and/or 4'-oxime formation. One compound was active against HIV at the micromolar range, and three compounds showed significant activity against the EBV lytic cycle at the medium-low nanomolar range. Among these derivatives, protoapigenone 1'-O-isopropyl ether (6) was identified as a promising lead that had a 73-times selectivity of antiviral over cytotoxic activity, which exceeds the selectivity of protoapigenone by 2.4-times. Our results open new opportunities for designing novel potent and safe anti-EBV agents that are based on the natural protoflavone moiety.

Synthesis of (11)C-labeled DNA polymerase-beta inhibitor 5-methoxyflavone and PET/CT imaging thereof.[Pubmed:31678783]

Nucl Med Biol. 2019 Nov - Dec;78-79:17-22.

INTRODUCTION: "Cell-cycle hypothesis" is emerging in recent years to suggest that aberrant cell cycle re-entry of differentiated neurons leads to a remarkable genetic disequilibrium which is likely to be the primary cause of neuronal apoptosis. DNA polymerase-beta is involved in neuronal DNA replication during cell cycle re-entry, thus constituting a promising target for Alzheimer's disease treatment. Recently, 5-methoxyflavone was identified as a candidate molecule endowed with good biological activity and selectivity on the DNA pol-beta in multiple in vitro AD models. In vivo assays, especially the brain uptake of 5-methoxyflavone, is need to be evaluated for further development for AD treatment. We report herein the synthesis of (11)C-labeled 5-methoxyflavone, and the evaluation of in vivo properties of 5-[(11)C]methoxyflavone in rodents. METHODS: The strategy for synthesis of 5-[(11)C]methoxyflavone was developed by treating precursor 5-Hydroxyflavone with [(11)C]CH3I and KOH in anhydrous DMF. 5-[(11)C]Methoxyflavone was purified, then evaluated in mice by using PET/CT imaging. RESULTS: The 5-[(11)C]methoxyflavone was synthesized conveniently in an average decay corrected yield of 22% (n=3) with a radiochemical purity >99%. The average molar radioactivity of 5-[(11)C]methoxyflavone was 383GBq/mumol. The average concentration was 0.107mug/mL. PET/CT imaging in mice showed 5-[(11)C]methoxyflavone rapidly passed through the blood-brain barrier with 8.36+/-0.61%ID/g at 2min post injection, and the radioactivity accumulation in brain was still noticeable with 2.48+/-0.59%ID/g at 28min post injection. The clearance rate was 3.37 (brain2 min/brain28 min ratio). The blood and muscle uptakes were low. The lung displayed high initial uptake and subsequent rapid clearance, while the liver and kidney displayed a relatively slow clearance. Real-time imaging showed that 5-[(11)C]methoxyflavone accumulated immediately in the heart, then transferred to the liver and intestine, and was not observed in lower digestive tract. CONCLUSIONS: 5-[(11)C]Methoxyflavone was synthesized conveniently in one step. The results of PET/CT imaging in C57BL/6 mice suggested 5-[(11)C]methoxyflavone possesses appropriate pharmacokinetic properties and favorable brain uptake, thus being proved to be suitable for further development for AD treatment.

Human CYP1A1 inhibition by flavonoids.[Pubmed:31655123]

Toxicol In Vitro. 2020 Feb;62:104681.

Cytochrome P4501A1 (CYP1A1) is involved in the metabolism of several genotoxic/carcinogenic environmental xenobiotics including polycyclic aromatic hydrocarbons (PAHs) like benzo[a]pyrene. Several authors had proposed CYP1A inhibition as a plausible strategy for cancer chemoprevention. Using ethoxyresorufin O-deethylase activity (EROD), we tested the inhibitory properties of nine flavonoids: quercetin, miricetin, luteolin, fisetin, morin, kaempferol, 5-Hydroxyflavone (5-HF), 3-hydroxyflavone (3-HF), and flavone (F) against human recombinant CYP1A1. The last three compounds exerted the highest inhibitory effect with IC50 values of 0.07, 0.10 and 0.08muM respectively; the more hydroxyl-groups were present, the lower the potency of inhibition was. Biochemical characterization leads to the conclusion that flavone and its hydroxy derivatives are mixed-type inhibitors. In silico studies have shown that, Phe224 and other aromatic residues in the human CYP1A1 active site play an important role in flavonoid-CYP interaction, through a pi/pi stacking between the aminoacid and the flavonoid C-ring. Outside the active site, the three flavonoids bind preferentially between A and K helices of the enzyme. Results from the Ames test using human S9 fraction revealed that none of the three compounds was mutagenic. We can consider 5-HF, 3-HF, and F as potential chemopreventive agents against genotoxic damage caused by metabolites resulting from CYP1A1 activity.

Oxidation of Flavone, 5-Hydroxyflavone, and 5,7-Dihydroxyflavone to Mono-, Di-, and Tri-Hydroxyflavones by Human Cytochrome P450 Enzymes.[Pubmed:30964977]

Chem Res Toxicol. 2019 Jun 17;32(6):1268-1280.

Biologically active plant flavonoids, including 5,7-dihydroxyflavone (57diOHF, chrysin), 4',5,7-trihydroxyflavone (4'57triOHF, apigenin), and 5,6,7-trihydroxyflavone (567triOHF, baicalein), have important pharmacological and toxicological significance, e.g., antiallergic, anti-inflammatory, antioxidative, antimicrobial, and antitumorgenic properties. In order to better understand the metabolism of these flavonoids in humans, we examined the oxidation of flavone, 5-Hydroxyflavone (5OHF), and 57diOHF to various products by human cytochrome P450 (P450 or CYP) and liver microsomal enzymes. Individual human P450s and liver microsomes oxidized flavone to 6-hydroxyflavone, small amounts of 5OHF, and 11 other monohydroxylated products at different rates and also produced several dihydroxylated products (including 57diOHF and 7,8-dihydroxyflavone) from flavone. We also found that 5OHF was oxidized by several P450 enzymes and human liver microsomes to 57diOHF and further to 567triOHF, but the turnover rates in these reactions were low. Interestingly, both CYP1B1.1 and 1B1.3 converted 57diOHF to 567triOHF at turnover rates (on the basis of P450 contents) of >3.0 min(-1), and CYP1A1 and 1A2 produced 567triOHF at rates of 0.51 and 0.72 min(-1), respectively. CYP2A13 and 2A6 catalyzed the oxidation of 57diOHF to 4'57triOHF at rates of 0.7 and 0.1 min(-1), respectively. Our present results show that different P450s have individual roles in oxidizing these phytochemical flavonoids and that these reactions may cause changes in their biological and toxicological properties in mammals.

5-Hydroxy-7-methoxyflavone derivatives from Kaempferia parviflora induce skeletal muscle hypertrophy.[Pubmed:30680186]

Food Sci Nutr. 2018 Nov 20;7(1):312-321.

Skeletal muscle plays a critical role in locomotion and energy metabolism. Maintenance or enhancement of skeletal muscle mass contributes to the improvement of mobility and prevents the development of metabolic diseases. The extracts from Kaempferia parviflora rhizomes contain at least ten methoxyflavone derivatives that exhibit enhancing effects on ATP production and glucose uptake in skeletal muscle cells. In the present study, we investigated the effects of ten K. parviflora-derived methoxyflavone derivatives (six 5,7-dimethoxyflavone (DMF) derivatives and four 5-hydroxy-7-methoxyflavone (HMF) derivatives) on skeletal muscle hypertrophy. Murine C2C12 myotubes and senescence-accelerated mouse-prone 1 (SAMP1) mice treated with methoxyflavones were used as experimental models to determine the effects of HMF derivatives on myotube diameter and size and muscle mass. The four HMF derivatives, but not the six DMF derivatives, increased myotube diameter. The 5-Hydroxyflavone, 7-methoxyflavone, and 5,7-dihydroxyflavone had no influence on myotube size, a result that differed from HMF. Dietary administration of the mixture composed of the four HMF derivatives resulted in increase in the soleus muscle size and mass in SAMP1 mice. HMF derivatives also promoted protein synthesis in myotubes, and treatment with the intracellular Ca(2+) chelator BAPTA-AM, which depletes intracellular Ca(2+) levels, inhibited this promotion. Furthermore, BAPTA-AM inhibited HMF-promoted protein synthesis even when myotubes were incubated in Ca(2+)-free medium. These results indicate that HMF derivatives induce myotube hypertrophy and that both the 5-hydroxyl group and the 7-methoxy group in the flavones are necessary for myotube hypertrophy. Furthermore, these results suggest that HMF-induced protein synthesis requires intracellular Ca(2+), but not extracellular Ca(2+).

Biotransformations of Flavones and an Isoflavone (Daidzein) in Cultures of Entomopathogenic Filamentous Fungi.[Pubmed:29874813]

Molecules. 2018 Jun 5;23(6). pii: molecules23061356.

Entomopathogenic filamentous fungi of the genus Isaria are effective biocatalysts in the biotransformation of flavonoids as well as steroids. In the present study, the species Isariafumosorosea and Isariafarinosa isolated from the environment were used. Their catalytic capacity to carry out biotransformations of flavones-unsubstituted, with hydroxy- and amino-substituents as well as a hydroxylated isoflavone-was investigated. Biotransformations of flavone, 5-Hydroxyflavone, 6-hydroxyflavone, 7-hydroxyflavone, and daidzein resulted in the formation of O-methylglucosides, in the case of flavone and 5-Hydroxyflavone with additional hydroxylations. 7-Aminoflavone was transformed into two acetamido derivatives. The following products were obtained: From flavone(-)flavone 2'-O-beta-d-(4''-O-methyl)-glucopyranoside, flavone 4'-O-beta-d-(4''-O-methyl)-glucopyranoside and 3'-hydroxyflavone 4'-O-beta-d-(4''-O-methyl)-glucopyranoside; from 5-Hydroxyflavone(-)5-Hydroxyflavone 4'-O-beta-d-(4''-O-methyl)-glucopyranoside; from 6-hydroxyflavone(-)flavone 6-O-beta-d-(4''-O-methyl)-glucopyranoside; from 7-hydroxyflavone(-)flavone 7-O-beta-d-(4''-O-methyl)-glucopyranoside; from daidzein(-)daidzein 7-O-beta-d-(4''-O-methyl)-glucopyranoside; and from 7-aminoflavone(-)7-acetamidoflavone and 7-acetamido-4'-hydroxyflavone. Seven of the products obtained by us have not been previously reported in the literature.

From in silico to in vitro: a trip to reveal flavonoid binding on the Rattus norvegicus Kir6.1 ATP-sensitive inward rectifier potassium channel.[Pubmed:29736333]

PeerJ. 2018 May 2;6:e4680.

Background: ATP-sensitive inward rectifier potassium channels (Kir), are a potassium channel family involved in many physiological processes. KATP dysfunctions are observed in several diseases such as hypoglycaemia, hyperinsulinemia, Prinzmetal angina-like symptoms, cardiovascular diseases. Methods: A broader view of the KATP mechanism is needed in order to operate on their regulation, and in this work we clarify the structure of the Rattus norvegicus ATP-sensitive inward rectifier potassium channel 8 (Kir6.1), which has been obtained through a homology modelling procedure. Due to the medical use of flavonoids, a considerable increase in studies on their influence on human health has recently been observed, therefore our aim is to study, through computational methods, the three-dimensional (3D) conformation together with mechanism of action of Kir6.1 with three flavonoids. Results: Computational analysis by performing molecular dynamics (MD) and docking simulation on rat 3D modelled structure have been completed, in its closed and open conformation state and in complex with Quercetin, 5-Hydroxyflavone and Rutin flavonoids. Our study showed that only Quercetin and 5-Hydroxyflavone were responsible for a significant down-regulation of the Kir6.1 activity, stabilising it in a closed conformation. This hypothesis was supported by in vitro experiments demonstrating that Quercetin and 5-Hydroxyflavone were capable to inhibit KATP currents of rat tail main artery myocytes recorded by the patch-clamp technique. Conclusion: Combined methodological approaches, such as molecular modelling, docking and MD simulations of Kir6.1 channel, used to elucidate flavonoids intrinsic mechanism of action, are introduced, revealing a new potential druggable protein site.

Decoding Surface Interaction of V(IV)O Metallodrug Candidates with Lysozyme.[Pubmed:29613772]

Inorg Chem. 2018 Apr 16;57(8):4456-4469.

The interaction of metallodrugs with proteins influences their transport, uptake, and mechanism of action. In this study, we present an integrative approach based on spectroscopic (EPR) and computational (docking) tools to elucidate the noncovalent binding modes of various V(IV)O compounds with lysozyme, a prototypical model of protein receptor. Five V(IV)O-flavonoid drug candidates formed by quercetin (que), morin (mor), 7,8-dihydroxyflavone (7,8-dhf), chrysin (chr), and 5-Hydroxyflavone (5-hf)-effective against several osteosarcoma cell lines-and two benchmark V(IV)O species of acetylacetone (acac) and catechol (cat) are evaluated. The results show a gradual variation of the EPR spectra at room temperature, which is associated with the strength of the interaction between the square pyramidal complexes [VOL2] and the surface residues of lysozyme. The qualitative strength of the interaction from EPR is [VO(que)2](2-) approximately [VO(mor)2] > [VO(7,8-dhf)2](2-) > [VO(chr)2] approximately [VO(5-hf)2] > [VO(acac)2] approximately [VO(cat)2](2-). This observation is compared with protein- ligand docking calculations with GOLD software examining the GoldScore scoring function ( F), for which hydrogen bond and van der Waals contact terms have been optimized to account for the surface interaction. The best predicted binding modes display an energy trend in good agreement with the EPR spectroscopy. Computation indicates that the strength of the interaction can be predicted by the Fmax value and depends on the number of OH or CO groups of the ligands that can interact with different sites on the protein surface and, more particularly, with those in the vicinity of the active site of the enzyme. The interaction strength determines the type of signal revealed ( rigid limit, slow tumbling, or isotropic) in the EPR spectra. Spectroscopic and computational results also suggest that there are several sites with comparable binding energy, with the V complexes distributing among them in a bound state and in aqueous solution in an unbound state. This kind of study and analysis could be generalized to determine the noncovalent binding modes of a generic metal species with a generic protein.

Flavonoid glycosides from leaves and straw of Oryza sativa and their effects of cytotoxicity on a macrophage cell line and allelopathic on weed germination.[Pubmed:29556129]

Saudi Pharm J. 2018 Mar;26(3):375-387.

Five new flavonoids namely, 5-hydroxy-6-isoprenyl-7,4'-dimethoxyflavonol-3-O-beta-d-arabinofuranoside (1), 5,7-dihydroxy-4'-methoxyflavone-7-O-beta-d-arabinopyranosyl-2''-n-decan-1'''-oate (2), 3-butanoyl-5,6,8-trihydroxy-7,4'-dimethoxyflavonol--5-O-beta-d-glucopyranoside (3), 7, 4'-dimethoxy-5-Hydroxyflavone-5-O-alpha-d-arabinopyranosyl-(2''-->1''')-O-alpha-d -arabinopyranoside (4), and 5,6-dihydroxy-7, 4'-dimethoxyflavone-5-O-alpha-d-glucopyranoside (5), together with two known compounds, were isolated from the methanol extract of Oryza sativa leaves and straw. Their structures of new compounds were elucidated by 1D and 2D NMR spectral methods, viz: COSY, HMBC and HSQC aided by mass techniques and IR spectroscopy. The cytotoxicity of these compounds (1-7) were assessed by using (RAW 264.7) mouse macrophages cell line, and allelopathic effects of compounds (1-7) on the germination characteristics of barnyardgrass (Echinochloa oryzicola) and pigweed (Chenopodium album L.) were also evaluated. The compounds 1, 6 and 7 showed cytotoxicity and compounds 1-7 exhibited significant inhibitory activity on the seed germination of two weed species.

Protective Mechanism of the Antioxidant Baicalein toward Hydroxyl Radical-Treated Bone Marrow-Derived Mesenchymal Stem Cells.[Pubmed:29361712]

Molecules. 2018 Jan 20;23(1). pii: molecules23010223.

Our study explores the antioxidant and cytoprotective effects of baicalein and further discusses the possible mechanisms. A methyl thiazolyl tetrazolium (MTT) assay revealed that baicalein could considerably enhance the viability of hydroxyl radical-treated bone marrow-mesenchymal stem cells (bmMSCs) at 37-370 microM. The highest viability rate was 120.4%. In subsequent studies, baicalein was observed to effectively scavenge hydroxyl radical and PTIO* radicals, reducing Fe(3+) and Cu(2+) ions. In the Fe(2+)-chelating UV-vis spectra, mixing of baicalein with Fe(2+) yielded two evident redshifts (275 --> 279 nm and 324 --> 352 nm) and a broad absorption peak (lambdamax approximately 650 nm, epsilon = 1.6 x 10(3) L mol(-1).cm(-1)). Finally, we compared the Fe(2+)-chelating UV-vis spectra of baicalein and its analogues, including 5-Hydroxyflavone, 6-hydroxyflavone, 7-hydroxyflavone, catechol, pyrogallol, and chrysin. This analysis revealed that the 4-keto group of the C-ring played a role. The 5,6,7-trihydroxy-group (pyrogallol group) in the A-ring served as an auxochrome, enhancing the absorbance of the UV-vis spectra and deepening the color of the Fe(2+)-complex. We concluded that baicalein, as an effective hydroxyl radical-scavenger, can protect bmMSCs from hydroxyl radical-mediated oxidative stress. Its hydroxyl radical-scavenging effects are likely exerted via two pathways: direct scavenging of hydroxyl radicals, possibly through electron transfer, and indirect inhibition of hydroxyl radical generation via Fe(2+) chelation through the 4-keto-5,6,7-trihydroxy groups.

Infrared spectroscopy of flavones and flavonols. Reexamination of the hydroxyl and carbonyl vibrations in relation to the interactions of flavonoids with membrane lipids.[Pubmed:29220817]

Spectrochim Acta A Mol Biomol Spectrosc. 2018 Mar 5;192:473-486.

Detailed vibrational assignments for twelve flavonoids (seven flavones (flavone, 3- and 5-Hydroxyflavone, chrysin, apigenin, fisetin and luteolin) and five flavonols (galangin, kaempferol, quercetin, morin and myricetin)) have been made based on own and reported experimental data and calculations at the B3LYP/6-31+G(d,p) level of theory. All the molecules are treated in a uniform way by using the same set of redundancy-free set of internal coordinates. A generalized harmonic mode mixing is used to corroborate the vibrational characteristics of this important class of molecules. Each flavonoid molecule can be treated from the vibrational point of view as made of relatively weakly coupled chromone and phenyl part. It has been shown that the strongest band around 1600cm(-1) need not be attributable to the CO stretching. The way the vibrations of any of the hydroxyl groups are mixed with ring vibrations and vibrations of other neighboring hydroxyl groups is rather involved. This imposes severe limitations on any attempt to describe normal modes of a flavonol in terms of hydroxyl or carbonyl group vibrations. The role of water molecules in the appearance of flavonoid IR spectra is emphasized. Knowing for the great affinity of phosphate groups in lipids towards water, the immediate consequence is a reasonable assumption that flavonoid lipid interactions is mediated by water.