6-Hydroxyflavanone

Development of flavanone and its derivatives as topical agents against psoriasis: The prediction of therapeutic efficiency through skin permeation evaluation and cell-based assay.[Pubmed:32220586]

Int J Pharm. 2020 May 15;581:119256.

Flavonoids inhibit skin inflammation. Previous study suggests that the flavonoids with flavanone backbone were beneficial to penetrate into the skin. We aimed to investigate the possibility of psoriasis treatment by topically applied flavanone and its derivatives including naringenin, hesperetin, 6-Hydroxyflavanone, flavanone, and 6-bromoflavone. The skin absorption of the compounds was determined by Franz cells. Molecular modeling was used to compute the physicochemical and molecular parameters of the penetrants in order to elucidate the correlation between structure and permeation. Among the compounds tested, flavanone showed the greatest skin absorption. The in vitro skin absorption predicted efficient skin targeting of 6-bromoflavone with minimal risk of circulation absorption. The permeation of naringenin was remarkably enhanced 13-fold in the barrier-defective skin mimicking inflamed skin. The penetrants with fewer hydrogen bond number, total polarity surface, and molecular volume were advantageous for facile skin absorption. In the cell-based study, IL-1beta inhibition in imiquimod (IMQ)-stimulated keratinocytes was increased following the increase in compound lipophilicity. Naringenin, a flavanone analog with three hydroxyl moieties, could suppress IL-6 overexpression to baseline control. We assessed the anti-inflammatory potency of the chemicals in comparison with tacrolimus as reference in a psoriasis-like mouse model. Flavanone was found to mitigate scaling and epidermal hyperplasia at a higher level than naringenin. Flavanone lessened IL-6 overexpression by 80% in the psoriasiform plaque. The skin barrier function recorded by transepidermal water loss (TEWL) was recovered by naringenin but not flavanone. The experimental data indicate that naringenin and flavanone are potential candidates for anti-psoriatic therapy.

Position Impact of Hydroxy Groups on Spectral, Acid-Base Profiles and DNA Interactions of Several Monohydroxy Flavanones.[Pubmed:31443449]

Molecules. 2019 Aug 22;24(17). pii: molecules24173049.

Structure-related biological activities of flavanones are still considered largely unexplored. Since they exhibit various medicinal activities, it is intriguing to enter deeper into their chemical structures, electronic transitions or interactions with some biomolecules in order to find properties that allow us to better understand their effects. Little information is available on biological activity of flavanone and its monohydroxy derivatives in relation to their physicochemical properties as spectral profiles, existence of protonated/deprotonated species under pH changes or interaction with Calf Thymus DNA. We devoted this work to research demonstrating differences in the physicochemical properties of the four flavanones: flavanone, 2'-hydroxyflavanone, 6-Hydroxyflavanone and 7-hydroxyflavanone and linking them to their biological activity. Potentiometric titration, UV-Vis spectroscopy were used to investigate influence of pH on acid-base and spectral profiles and to propose the mode of interaction with DNA. Cyclic voltammetry was applied to evaluate antioxidant potentiality and additionally, theoretical DFT(B3LYP) method to disclose electronic structure and properties of the compounds. Molecular geometries, proton affinities and pKa values have been determined. According to computational and cyclic voltammetry results we could predict higher antioxidant activity of 6-Hydroxyflavanone with respect to other compounds. The values of Kb intrinsic binding constants of the flavanones indicated weak interactions with DNA. Structure-activity relationships observed for antioxidant activity and DNA interactions suggest that 6-Hydroxyflavanone can protect DNA against oxidative damage most effectively than flavanone, 2'-hydroxyflavanone or 7-hydroxyflavanone.

Antityrosinase, Antioxidant, and Cytotoxic Activities of Phytochemical Constituents from Manilkara zapota L. Bark.[Pubmed:31370334]

Molecules. 2019 Jul 31;24(15). pii: molecules24152798.

Hyperpigmentation is considered by many to be a beauty problem and is responsible for photoaging. To treat this skin condition, medicinal cosmetics containing tyrosinase inhibitors are used, resulting in skin whitening. In this study, taraxerol methyl ether (1), spinasterol (2), 6-Hydroxyflavanone (3), (+)-dihydrokaempferol (4), 3,4-dihydroxybenzoic acid (5), taraxerol (6), taraxerone (7), and lupeol acetate (8) were isolated from Manilkara zapota bark. Their chemical structures were elucidated by analysis of their nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) data, and by comparing them with data found in the literature. The in vitro antityrosinase, antioxidant, and cytotoxic activities of the isolated compounds (1-8) were evaluated. (+)-Dihydrokaempferol (4) exhibited higher monophenolase inhibitory activity than both kojic acid and alpha-arbutin. However, it showed diphenolase inhibitory activity similar to kojic acid. (+)-Dihydrokaempferol (4) was a competitive inhibitor of both monophenolase and diphenolase activities. It exhibited the strongest 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and ferric reducing antioxidant power (FRAP) activities of the isolated compounds. Furthermore, (+)-dihydrokaempferol (4) also demonstrated potent cytotoxicity in breast carcinoma cell line (BT474), lung bronchus carcinoma cell line (Chago-K1), liver carcinoma cell line (HepG2), gastric carcinoma cell line (KATO-III), and colon carcinoma cell line (SW620). These results suggest that M. zapota bark might be a good potential source of antioxidants and tyrosinase inhibitors for applications in cosmeceutical products.

Thiol-ene click derived structurally well-defined per(3,5-dimethyl)phenylcarbamoylated cationic cyclodextrin separation material for achiral and chiral chromatography.[Pubmed:29726105]

J Sep Sci. 2018 Jul;41(13):2710-2718.

In this work, a novel single sulfoether-bridged cationic per(3,5-dimethyl)phenylcarbamoylated-beta-cyclodextrin separation material was prepared by thiol-ene click chemistry and characterized by using FTIR spectroscopy, solid-state (13) C NMR spectroscopy and elemental analysis, which confirmed the correct structure. The separation material exhibited a good achiral separation performance for benzene homologues and phenylamine analogs, especially o-xylene and m-xylene, and m-phenylenediamine and o-phenylenediamine can be discriminated by the (3,5-dimethyl)phenylcarbamoyl cyclodextrins. The chiral resolving ability of the separation material was evaluated by discriminating various isoxazolines, flavonoids, and beta-blockers in reversed-phase high-performance liquid chromatography. For isoxazolines, the material showed the best chiral discrimination toward 3-aryl-5-(2-oxopyrrolidin-1-yl)-isoxazolines, where the resolution for 3ClPh-OPr reached 6.03. For flavonoids, it exhibited more efficient separation to the ones with more hydrophobic substituents, with a resolution of 5.93 for 6-Hydroxyflavanone. beta-Blockers were also enantioseparated satisfactorily on the material. The as-prepared separation material is a good member of the thiol-ene click derived cyclodextrin stationary phase family.

Ordered mesoporous silica functionalized with beta-cyclodextrin derivative for stereoisomer separation of flavanones and flavanone glycosides by nano-liquid chromatography and capillary electrochromatography.[Pubmed:28202192]

J Chromatogr A. 2017 Mar 24;1490:166-176.

In this paper a chiral stationary phase (CSP) was prepared by the immobilization of a beta-CD derivative (3,5-dimethylphenylcarbamoylated beta-CD) onto the surface of amino-functionalized spherical ordered mesoporous silica (denoted as SM) via a urea linkage using the Staudinger reaction. The CSP was packed into fused silica capillaries 100mum I.D. and evaluated by means of nano-liquid chromatography (nano-LC) and capillary electrochromatography (CEC) using model compounds for the enantio- and the diastereomeric separation. The compounds flavanone, 2'-hydroxyflavanone, 4'-hydroxyflavanone, 6-Hydroxyflavanone, 4'-methoxyflavanone, 7-methoxyflavanone, hesperetin, hesperidin, naringenin, and naringin were studied using reversed and polar organic elution modes. Baseline stereoisomer resolution and good results in terms of peak efficiency and short analysis time of all studied flavonoids and flavanones glycosides were achieved in reversed phase mode, using as mobile phase a mixture of MeOH/H2O, 10mM ammonium acetate pH 4.5 at different ratios. For the polar organic mode using 100% of MeOH as mobile phase, the CSP showed better performances and the baseline chiral separation of several studied compounds occurred in an analysis time of less than 10min. Good results were also achieved by CEC employing two different mobile phases. The use of MeOH/H2O, 5mM ammonium acetate buffer pH 6.0 (90/10, v/v) was very effective for the chiral resolution of flavanone and its methoxy and hydroxy derivatives.

[Study on Fluorescence Properties of Flavanone and Its Hydroxyl Derivatives].[Pubmed:30048098]

Guang Pu Xue Yu Guang Pu Fen Xi. 2016 Apr;36(4):1007-12.

Flavanone derivatives are important active ingredients of natural medicine, so the synthesis of these compounds is one of the research hotspots of organic synthesis. Nevertheless, there is little research on fluorescence properties of these compounds up to now. Fluorescence properties of flavanone and 6 kinds of hydroxyl derivatives are studied in this paper. It is found that aqueous solutions of flavanone (FV), 7-hydroxyflavanone (7HF) and 6-Hydroxyflavanone (6HF) have fluorescence, but aqueous solutions of 2'-hydroxyflavanone (2'HF), 4'-hydroxyflavanone (4'HF), naringenin and pinocembrin basically have no fluorescence. In three dimensional fluorescence spectra, excitation wavelengths lambdaex of FV are located at 235, 265 and 340 nm, emission wavelength lambdaem is at 386 nm; lambdaex of 7HF are at 230, 276 and 315 nm, lambdaem is at 391 nm; lambdaex of 6HF are at 260 and 356 nm, em is at 482 nm. Influences of pH on fluorescence of FV, 7HF and 6HF are studied, and the reasons of pH affects on fluorescence are discussed from the viewpoint of molecular structure. The UV-absorption spectra of 7HF and 6HF at different pH are studied, and the proton ionization constants (pKa) of 7HF and 6HF are determined respectively to be 7.26+/-0.05 and 9.90+/-0.02, by a pH-absorption method. Influences of solvent (methanol) on fluorescence of FV, 7HF and 6HF are studied, and find that the fluorescence of FV and 7HF in methanol are weaker than that in water, but the fluorescence of 6HF in methanol is much stronger. In ordered media (SDS, CTAB and beta-CD), fluorescence of FV and 7HF decreased than that in water, but the fluorescence of 6HF enhanced in the media of beta-CD or CTAB. Using quinine sulfate or L-tryptophane as reference, fluorescence quantum yields of FV and 7HF aqueous solutions are measured to be 0.057 and 0.012, respectively; fluorescence quantum yields of 6HF in methanol or in aqueous solution containing 1.62 mg.mL-1 beta-CD are measured to be 0.064 or 0.012, respectively.

Eleven Microbial Metabolites of 6-Hydroxyflavanone.[Pubmed:26235165]

Chem Pharm Bull (Tokyo). 2015;63(8):579-83.

6-Hydroxyflavanone (1) when fermented with fungal culture Cunninghamella blakesleeana (ATCC 8688a) yielded flavanone 6-O-beta-D-glucopyranoside (2), flavanone 6-sulfate (3), and 6-Hydroxyflavanone 7-sulfate (4). Aspergillus alliaceus (ATCC 10060) also transformed 1 to metabolite 3 as well as 4'-hydroxyflavanone 6-sulfate (5) and 6,4'-dihydroxyflavanone (6). Beauveria bassiana (ATCC 7159) metabolized 1 to 6 and flavanone 6-O-beta-D-4-O-methyglucopyranoside (7). Mucor ramannianus (ATCC 9628) transformed 1 to 2,4-cis-6-hydroxyflavan-4-ol (8), 2,4-trans-6-hydroxyflavan-4-ol (9), 2,4-trans-6,4'-dihydroxyflavan-4-ol 5-sulfate (10), 1,3-cis-1-methoxy-1-(2,5-dihydroxyphenyl)-3-phenylpropane (11) and 2,4-trans-flavan-4-ol 6-sulfate (12). Structures of the metabolic products were elucidated by means of spectroscopic data. None of the metabolites tested showed antibacterial, antifungal and antimalarial activities against selected organisms. However, weak antileishmanial activity was observed for metabolite 11 when tested against Leishmania donovani.

Microbial biotransformation of bioactive flavonoids.[Pubmed:25447420]

Biotechnol Adv. 2015 Jan-Feb;33(1):214-223.

The bioactive flavonoids are considered as the most important phytochemicals in food, which exert a wide range of biological benefits for human being. Microbial biotransformation strategies for production of flavonoids have attracted considerable interest because they allow yielding novel flavonoids, which do not exist in nature. In this review, we summarize the existing knowledge on the production and biotransformation of flavonoids by various microbes. The main reactions during microbial biotransformation are hydroxylation, dehydroxylation, O-methylation, O-demethylation, glycosylation, deglycosylation, dehydrogenation, hydrogenation, C ring cleavage of the benzo-gamma-pyrone system, cyclization, and carbonyl reduction. Cunninghamella, Penicillium, and Aspergillus strains are very popular to biotransform flavonoids and they can perform almost all the reactions with excellent yields. Aspergillus niger is one of the most applied microorganisms in the flavonoids' biotransformation; for example, A. niger can transfer flavanone to flavan-4-ol, 2'-hydroxydihydrochalcone, flavone, 3-hydroxyflavone, 6-Hydroxyflavanone, and 4'-hydroxyflavanone. The hydroxylation of flavones by microbes usually happens on the ortho position of hydroxyl group on the A ring and C-4' position of the B ring and microbes commonly hydroxylate flavonols at the C-8 position. The microorganisms tend to hydroxylate flavanones at the C-5, 6, and 4' positions; however, for prenylated flavanones, dihydroxylation often takes place on the C4alpha=C5alpha double bond on the prenyl group (the side chain of A ring). Isoflavones are usually hydroxylated at the C-3' position of the B ring by microorganisms. The microbes convert flavonoids to their 7-O-glycosides and 3-O-glycosides (when flavonoids have a hydroxyl moiety at the C-3 position). The demethylation of multimethoxyl flavonoids by microbes tends to happen at the C-3' and C-4' positions of the B ring. Multimethoxyl flavanones and isoflavone are demethylated at the C-7 and C-4' positions. The O-methylation of flavonols happens at the C-3' and C-4' and microorganisms O-methylate flavones at the C-6 position and the O-methylation of flavanones, usually took place on the hydroxyl groups of the A ring. The prenyl flavanones were cyclized at the prenyl side chain to form a new five-member ring attached to the A ring. Chalcones were regioselectively cyclized to flavanones. Hydrogenation of flavonoids was only reported on transformation of chalcones to dihydrochalcones. The dehydrogenation of flavanoids to flavonoids was not comprehensively studied.

Conventional Chiralpak ID vs. capillary Chiralpak ID-3 amylose tris-(3-chlorophenylcarbamate)-based chiral stationary phase columns for the enantioselective HPLC separation of pharmaceutical racemates.[Pubmed:25271972]

Chirality. 2014 Nov;26(11):677-82.

A comparative enantioselective analysis using immobilized amylose tris-(3-chlorophenylcarbamate) as chiral stationary phase in conventional high-performance liquid chromatography (HPLC) with Chiralpak ID (4.6 mm ID x 250 mm, 5 microm silica gel) and micro-HPLC with Chiralpak ID-3 (0.30 mm ID x 150 mm, 3 microm silica gel) was conducted. Pharmaceutical racemates of 12 pharmacological classes, namely, alpha- and beta-blockers, anti-inflammatory drugs, antifungal drugs, dopamine antagonists, norepinephrine-dopamine reuptake inhibitors, catecholamines, sedative hypnotics, diuretics, antihistaminics, anticancer drugs, and antiarrhythmic drugs were screened under normal phase conditions. The effect of an organic modifier on the analyte retentions and enantiomer recognition was investigated. Baseline separation was achieved for 1-acenaphthenol, carprofen, celiprolol, cizolirtine carbinol, miconazole, tebuconazole, 4-hydroxy-3-methoxymandelic acid, 1-indanol, 1-(2-chlorophenyl)ethanol, 1-phenyl-2-propanol, flavanone, 6-Hydroxyflavanone, 4-bromogluthethimide, and pentobarbital on the 4.6 mm ID packed with a 5 microm silica column using conventional HPLC. Nonetheless, baseline separation was achieved for aminoglutethimide, naftopidil, and thalidomide on the 0.3 mm ID packed with a 3 microm silica capillary column.

Synthetic flavanones augment the anticancer effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).[Pubmed:23027370]

Molecules. 2012 Oct 1;17(10):11693-711.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered as the most promising anticancer agent in the TNF superfamily because of its selective cytotoxicity against tumor cells versus normal primary cells. However, as more tumor cells are reported to be resistant to TRAIL-mediated death, it is important to develop new therapeutic strategies to overcome this resistance. Flavonoids have been shown to sensitize cancer cells to TRAIL-induced apoptosis. The aim of this study was to examine the cytotoxic and apoptotic activities of TRAIL on HeLa cancer cells in combination with two synthetic compounds: 6-Hydroxyflavanone (6-HF) and its derivative 6-propionoxy-flavanone (6-PF) and to determine the mechanism by which the flavanones overcome the TRAIL-resistance. The cytotoxicity was measured by MTT and LDH assays. The apoptosis was detected by annexin V-FITC fluorescence staining in flow cytometry and microscopy. Death receptor (TRAIL-R1/DR4 and TRAIL-R2/DR5) expression were analysed using flow cytometry. Mitochondrial membrane potential was evaluated using DePsipher staining by fluorescence microscopy. The synthetic flavanones enhanced TRAIL-induced apoptosis in HeLa cells through increased expression of TRAIL-R2 death receptor and reduction of mitochondrial membrane potential. Our study indicates that the 6-HF and 6-PF augmented the anticancer effects of TRAIL and confirm a potential use of flavanones in TRAIL-based anticancer therapy and prevention.

Bioconversion of 7-hydroxyflavanone: isolation, characterization and bioactivity evaluation of twenty-one phase I and phase II microbial metabolites.[Pubmed:22976322]

Chem Pharm Bull (Tokyo). 2012;60(9):1139-45.

Microbial metabolism of 7-hydroxyflavanone (1) with fungal culture Cunninghamella blakesleeana (ATCC 8688a), yielded flavanone 7-sulfate (2), 7,4'-dihydroxyflavanone (3), 6,7-dihydroxyflavanone (4), 6-Hydroxyflavanone 7-sulfate (5), and 7-hydroxyflavanone 6-sulfate (6). Mortierella zonata (ATCC 13309) also transformed 1 to metabolites 2 and 3 as well as 4'-hydroxyflavanone 7-sulfate (7), flavan-4-cis-ol 7-sulfate (8), 2',4'-dihydroxychalcone (9), 7,8-dihydroxyflavanone (10), 8-hydroxyflavanone 7-sulfate (11), and 8-methoxy-7-hydroxyflavanone (12). Beauveria bassiana (ATCC 7159) metabolized 1 to 2, 3, and 8, flavanone 7-O-beta-D-O-4-methoxyglucopyranoside (13), and 8-hydroxyflavanone 7-O-beta-D-O-4-methoxyglucopyranoside (14). Chaetomium cochlioides (ATCC 10195) also transformed 1 to 2, 3, 9, together with 7-hydroxy-4-cis-ol (15). Mucor ramannianus (ATCC 9628) metabolized 1 in addition to 7, to also 4,2',4'-trihydroxychalcone (16), 7,3',4'-trihydroxyflavanone (17), 4'-hydroxyflavanone 7-O-alpha-L-rhamnopyranoside (18), and 7,3',4'-trihydroxy-6-methoxyflavanone (19). The organism Aspergillus alliaceus (ATCC 10060) transformed 1 to metabolites 3, 16, 7,8,4'-trihydroxyflavanone (20), and 7-hydroxyflavanone 4'-sulfate (21). A metabolite of 1, flavanone 7-O-beta-D-O-glucopyranoside (22) was produced by Rhizopus oryzae (ATCC 11145). Structures of the metabolic products were elucidated by means of spectroscopic data. None of the metabolites tested showed antibacterial, antifungal and antimalarial activities against selected organisms. Metabolites 4 and 16 showed weak antileishmanial activity.

Evaluation of novel amylose and cellulose-based chiral stationary phases for the stereoisomer separation of flavanones by means of nano-liquid chromatography.[Pubmed:22790704]

Anal Chim Acta. 2012 Aug 13;738:85-94.

Three polysaccharide-based chiral stationary phases, Sepapak((R)) 1, Sepapak((R)) 2 and Sepapak((R)) 3 have been evaluated in the present work for the stereoisomer separation of a group of 12 flavonoids including flavanones (flavanone, 4'-methoxyflavanone, 6-methoxyflavanone, 7-methoxyflavanone, 2'-hydroxyflavanone, 4'-hydroxyflavanone, 6-Hydroxyflavanone, 7-hydroxyflavanone, hesperetin, naringenin) and flavanone glycosides (hesperidin, naringin) by nano-liquid chromatography (nano-LC). The behaviour of these chiral stationary phases (CSPs) towards the selected compounds was studied in capillary columns (100mum internal diameter (i.d.)) packed with the above mentioned CSPs using polar organic, reversed and normal elution modes. The influence of nature and composition of the mobile phase in terms of concentration and type of organic modifier, buffer type and water content (reversed phase elution mode) on the enantioresolution (R(s)), retention factor (k) and enantioselectivity (alpha) was evaluated. Sepapak((R)) 3 showed the best chromatographic results in terms of enantioresolution, enantioselectivity and short analysis time, employing a polar organic phase mode. A mixture of methanol/isopropanol (20/80, v/v) as mobile phase enabled the chiral separation of eight flavanones with enantioresolution factor (R(s)) in the range 1.15-4.18. The same analytes were also resolved employing reversed and normal phase modes with mixtures of methanol/water and hexane/ethanol at different ratios as mobile phases, respectively. Loss in resolution for some compounds, broaden peaks and longer analysis times were observed with these last two chromatographic elution modes. Afterwards, a comparison with the other two CSPs was performed. A lower discrimination ability of Sepapak((R)) 1 and Sepapak((R)) 2 towards all the studied flavanoids was observed. However, Sepapak((R)) 1 allowed the separation of naringenin enantiomers and naringin stereoisomers in polar organic phase which were not resolved with the other two CSPs. The nature of the chiral selector was found to be of utmost importance for the resolution of the selected compounds. Indeed, significant differences in enantioresolution among the three tested CSPs were observed. With regard to the only few data reported in the literature for the resolution of this class of compounds using polysaccharide-based CSPs by high performance liquid chromatography (HPLC), the results obtained in this study by means of nano-LC showed higher (R(s)) values and shorter analysis time.

Physicochemical characterization and antioxidant activity of melanin from a novel strain of Aspergillus bridgeri ICTF-201.[Pubmed:21726247]

Lett Appl Microbiol. 2011 Sep;53(3):350-8.

AIMS: The aim of the study is to isolate and characterize a melanin pigment from a new strain of Aspergillus bridgeri isolated from rhizosphere soil of Eucalyptus tree and to investigate its antioxidant activity. METHODS AND RESULTS: The extracellular pigment was alkali soluble, acid-resistant and insoluble in organic solvents and water. The pigment was precipitated on treatment with FeCl(3), ammoniacal AgNO(3) and potassium ferricyanide and was bleached in the presence of oxidants and reductants. It was confirmed as melanin based on the Fourier transform infrared and electron paramagnetic resonance spectroscopy techniques apart from chemical analysis. Inhibition of melanin production by inhibitors like tricyclazole, 6-Hydroxyflavanone, 4-hydroxy-7-methoxy-3-phenyl-coumarin, 7-hydroxy-4-phenyl-coumarin and 7-hydroxy-3,4,8-trimethylcoumarin confirmed that melanin produced by A. bridgeri is synthesized by 1,8-dihydroxynaphthalene (DHN)-melanin pathway. The melanin showed good free radical scavenging activity by DPPH method with an EC(50) of 54.12 mug ml(-1). CONCLUSIONS: The results of the study indicate that the melanin produced by the newly isolated A. bridgeri strain is a member of DHN melanin family and exhibited significant free radical scavenging activity. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report on characterization of DHN melanin produced by a novel strain of A. bridgeri and may find potential application as a natural antioxidant in the cosmetic and pharmaceutical industries.

Optical isomer separation of flavanones and flavanone glycosides by nano-liquid chromatography using a phenyl-carbamate-propyl-beta-cyclodextrin chiral stationary phase.[Pubmed:19699481]

J Chromatogr A. 2010 Feb 12;1217(7):1175-82.

In this paper a phenyl-carbamate-propyl-beta-cyclodextrin stationary phase was employed for the enantioseparation of several flavonoids, including flavanones and methoxyflavanones by using nano-liquid chromatography (nano-LC). The same stationary phase was also used for the diastereoisomeric separation of two flavanone glycosides. The compounds: flavanone, 2'-hydroxyflavanone, 4'-hydroxyflavanone, 6-Hydroxyflavanone, 7-hydroxyflavanone, 4'-methoxyflavanone, 6-methoxyflavanone, 7-methoxyflavanone, hesperetin, hesperidin, naringenin and naringin were studied using reversed, polar organic and normal elution modes. The effect of the nature and composition of the mobile phase (organic modifier type, buffer and water content in the reversed phase mode) on the enantioresolution (R(s)), retention factor (k) and enantioselectivity (alpha) were investigated. Baseline resolution of all studied flavonoids, with the exception of 2'-hydroxyflavanone and naringin, was achieved in reversed phase mode using a mixture of MeOH/H(2)O at different ratios as mobile phase. Good results, in terms of peak efficiency and short analysis time, were obtained adding 1% triethylammonium acetate pH 4.5 buffer to MeOH/H(2)O mixture. The separation of the studied compounds was also performed in polar organic mode. By using 100% of MeOH as mobile phase, the resolution was achieved for the studied analytes, except for 7-hydroxyflavanone, 2'-hydroxyflavanone, naringenin, hesperidin and naringin. Normal mode was tested employing a mixture of EtOH/hexane/TFA as mobile phase achieving the enantiomeric and diastereomeric separation of only hesperetin and hesperidin, respectively. The use of nano-LC technique for the resolution of flavanones optical isomers allowed to achieve good resolutions in shorter analysis time compared to the results reported in literature with conventional HPLC.

Microbial metabolism part 9. Structure and antioxidant significance of the metabolites of 5,7-dihydroxyflavone (chrysin), and 5- and 6-hydroxyflavones.[Pubmed:18379084]

Chem Pharm Bull (Tokyo). 2008 Apr;56(4):418-22.

5,7-Dihydroxyflavone (chrysin) (1) when fermented with fungal cultures, Aspergillus alliaceous (ATCC 10060), Beauveria bassiana (ATCC 13144) and Absidia glauco (ATCC 22752) gave mainly 4'-hydroxychrysin (4), chrysin 7-O-beta-D-4-O-methylglucopyranoside (5) and chrysin 7-sulfate (6), respectively. Mucore ramannianus (ATCC 9628), however, transformed chrysin into six metabolites: 4'-hydroxy-3'-methoxychrysin (chrysoeriol) (7), 4'-hydroxychrysin (apigenin) (4) 3',4'-dihydroxychrysin (luteolin) (8), 3'-methoxychrysin 4'-O-alpha-D-6-deoxyallopyranoside (9), chrysin 4'-O-alpha-D-6-deoxyallopyranoside (10), and luteolin 3'-sulfate (11). Cultures of A. alliaceous (ATCC 10060) and B. bassiana (ATCC 13144) metabolized 5-hydroxyflavone (2) into 5,4'-dihydroxyflavone (12) and 4'-hydroxyflavone 5-O-beta-D-4-O-methylglucopyranoside (13), respectively. 6-Hydroxyflavone (3) was transformed into 6-Hydroxyflavanone (14), flavone 3-O-beta-D-4-O-methylglucopyranoside (15) and (+/-)-flavanone 6-O-beta-D-4-O-methylglucopyranoside (16) by cultures of Beauveria bassiana (ATCC 13144). The structures of the metabolic products were elucidated by means of spectroscopic data. The significance of the metabolites as antioxidants in relation to their structure is briefly discussed.