Showing papers on "Glucoside published in 2018"

The Intracellular Localization of the Vanillin Biosynthetic Machinery in Pods of Vanilla planifolia.

Abstract: Vanillin is the most important flavor compound in the vanilla pod. Vanilla planifolia vanillin synthase (VpVAN) catalyzes the conversion of ferulic acid and ferulic acid glucoside into vanillin and vanillin glucoside, respectively. Desorption electrospray ionization mass spectrometry imaging (DESI-MSI) of vanilla pod sections demonstrates that vanillin glucoside is preferentially localized within the mesocarp and placental laminae whereas vanillin is preferentially localized within the mesocarp. VpVAN is present as the mature form (25 kDa) but, depending on the tissue and isolation procedure, small amounts of the immature unprocessed form (40 kDa) and putative oligomers (50, 75 and 100 kDa) may be observed by immunoblotting using an antibody specific to the C-terminal sequence of VpVAN. The VpVAN protein is localized within chloroplasts and re-differentiated chloroplasts termed phenyloplasts, as monitored during the process of pod development. Isolated chloroplasts were shown to convert [14C]phenylalanine and [14C]cinnamic acid into [14C]vanillin glucoside, indicating that the entire vanillin de novo biosynthetic machinery converting phenylalanine to vanillin glucoside is present in the chloroplast.

Activity-Guided Identification of in Vitro Antioxidants in Beer

Abstract: In order to locate the key antioxidants contributing to oxidative stability of beer, activity-guided fractionation in combination with the oxygen radical absorbance capacity (ORAC) assay, hydrogen peroxide scavenging (HPS) assay, and linoleic acid (LA) assay was applied to a pilsner-type beer. LC-MS and 1D/2D NMR experiments led to the identification of a total of 31 antioxidants, among which 3-methoxy-4-hydroxyphenyl-β-d-glucopyranoside (tachioside), 4-(2-formylpyrrol-1-yl)butyric acid, 4-[2-formyl-5-(hydroxymethyl)pyrrol-1-yl]butyric acid, n-multifidol-3-O-β-d-glucoside, quercetin-3-O-(6″-malonyl)-glucoside, 4-feruloylquinic acid, syringaresinol, saponarin, and hordatines A–C have been isolated from beer for the first time. On a molar comparison, the hordatines A–C, saponarin, and quercetin-3-O-β-d-(6″-malonyl)glucoside were evaluated with the highest antioxidant activities of all identified beer constituents, reaching values of 10–17.5 (ORAC), 2.0–4.1 (HPS), and 1.1–6.1 μmol TE/μmol (LA) for hordatines...

Recent progress on biological production of α-arbutin.

Abstract: Arbutin, a glucoside of hydroquinone, is used as a powerful skin lightening agent in the cosmeceutical industry because of its strong inhibitory effect on the human tyrosinase activity. It is a natural compound occurring in a number of plants, with a β-anomeric form of the glycoside bond between glucose and hydroquinone. α-Arbutin, which glycoside bond is generated with α-anomeric form, is the isomer of natural arbutin. α-Arbutin is generally produced by transglucosylation of hydroquinone by microbial glycosyltransferases. It is interesting that α-arbutin is found to be over 10 times more effective than arbutin, and thus biological production of α-arbutin attracts increasing attention. Seven different microbial enzymes have been identified to be able to produce α-arbutin, including α-amylase, sucrose phosphorlase, cyclodextrin glycosyltransferase, α-glucosidase, dextransucrase, amylosucrase, and sucrose isomerase. In this work, enzymatic and microbial production of α-arbutin is reviewed in detail.

Synthesis, activity, and docking studies of eugenol-based glucosides as new agents against Candida sp.

Abstract: Seventeen new synthetic derivatives of eugenol (6, 8-15 and 8'-15') were planned following literature reports on antifungal activities of nitroeugenol and eugenol glucoside. The anti-Candida activity of these compounds was investigated by in vitro assay, and the cytotoxicity evaluation was performed with the most active compounds. The peracetylated glucosides presented better biological results than their hydroxylated analogues. The glucoside 11, a 4-nitrobenzamide, showed the best potency (MIC50 range 11.0-151.84 μm), the wider spectrum of action, and overall the best selectivity indexes, especially against C. tropicalis (~30) and C. krusei (~15). To investigate its possible mechanism of action, glucoside 11 was subjected to molecular docking studies with Candida sp. enzymes involved in ergosterol biosynthesis. Results have shown that the peracetyl glucosyl moiety and the 4-nitrobenzamide group in 11 are effectively involved in its high affinity with the active site of squalene epoxidase.

HPLC-DAD-ESI-MS/MS characterization of bioactive secondary metabolites from Strelitzia nicolai leaf extracts and their antioxidant and anticancer activities In vitro

Abstract: Background: Strelitzia nicolai Regel and Korn (Strelitziaceae) is native to Southern Africa whose phytochemistry and pharmacology were slightly investigated. Materials and Methods: In the current work, different solvent extracts of S. nicolai were screened for their chemical profiles through high-performance liquid chromatography coupled with diode array detection and electrospray ionization mass spectrometry (HPLC-DAD-ESI-MS/MS) analyses. Furthermore, their in vitro antioxidant, cytotoxic, and anticancer activities were evaluated using 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) & ferric reducing antioxidant power (FRAP) and crystal violet staining (CVS) colorimetric assays, respectively. Results: HPLC-DAD-ESI-MS/MS analyses led to the identification of nineteen and eleven phenolic compounds from the ethyl acetate and n-butanol extracts, respectively including flavonoids (e.g., quercetin 3-(2 G-rhamnosylrutinoside, quercetin, quercetin-3-O-glucoside, kaempferol-3,7-O-dirhamnoside, isorhamnetin-3-O-rutinoside and kaempferol-3-O-glucoside), phenolic acids derivatives (e.g., chlorogenic acid glycoside, protocatechuic acid-O-glucoside and caftaric acid), chalcones (e.g., xanthoangelol), and phenylethanoids (e.g., ligstroside glucoside). Moreover, in the DPPH assay the IC50value of the most active ethyl acetate extract was 20.49 μg/mL, relative to 2.92 μg/mL of ascorbic acid. ABTS and FRAP results reinforced the results of DPPH assay. According to the National Cancer Institute criteria, the tested extracts showed weak to moderate cytotoxic activities with IC50values ranged from 65.23 to 451.29 μg/mL. Furthermore, the EtOAc and n-BuOH extracts showed a noticeable anticancer activity with CVS spectroscopic readings for liver hepatocellular carcinoma growth 0.806 and 0.684 at a concentration (125 μg/mL), as well as 0.730 and 0.618 at concentration (500 μg/mL), respectively against control at 1.022. Conclusion: The obtained results reveal the high efficacy of the phenolic-rich extracts from S. nicolai as naturally occurring antioxidant and anti-tumor agents. Abbreviations Used: HPLC-DAD-ESI-MS/MS: High-performance liquid chromatography-diode array detection-electrospray ionization-mass/mass; DPPH: 2,2'-Diphenyl-1-picrylhydrazyl radical; ABTS: 2,2'-Azino-bis (3-ethylbenzothiazoline-6-sulphonic acid); FRAP: Ferric reducing antioxidant power; TPTZ: Tripyridyl-s-triazine; FE: Ferrous equivalents; DMEM: Dulbecco's modified eagle's medium; DMSO: Dimethyl sulfoxide; EDTA: Ethylenediaminetetraacetic acid; PBS: Phosphate buffered saline; HepG-2: Liver hepatocellular carcinoma; CVS: Crystal violet stain; NCI: National cancer institute; Glu: Glucose; Rha: Rhamnose.

Enzymatic Synthesis of α-flavone Glucoside via Regioselective Transglucosylation by Amylosucrase From Deinococcus Geothermalis

Abstract: α-Flavone glycosides have beneficial properties for applications in the pharmaceutical, cosmetic, and food industries. However, their chemical syntheses are often limited by a low efficiency or scarcity of substrates. In this study, α-flavone glucosides were enzymatically synthesized by amylosucrase from Deinococcus geothermalis (DGAS) using sucrose and various flavones as a donor for glucosyl units and acceptors, respectively. Luteolin was the most effective acceptor in the transglucosylation reaction using DGAS among nine flavone materials (apigenin, chrysin, 6,7-dihydroxyflavone, homoorientin, 7-hydroxyflavone, isorhoifolin, luteolin, luteolin-3',7-diglucoside, and orientin). The highest production yield of luteolin glucoside was 86%, with a 7:1 molar ratio of donor to acceptor molecules, in 50 mM Tris-HCl buffer (pH 7) at 37°C for 24 h using 2 U of DGAS. The synthesized luteolin glucoside was identified as luteolin-4'-O-α-D-glucopyranoside with a glucose molecule linked to the C-4' position on the B-ring of luteolin via an α-glucosidic bond, as determined by 1H and 13C nuclear magnetic resonance. This result clearly confirmed that the glucosylated luteolin was successfully synthesized by DGAS and it can be applied as a functional ingredient. Furthermore, this approach using DGAS has the potential to be utilized for the synthesis of various glucosylated products using different types of polyphenols to enhance their functionalities.

Vanillin production by biotransformation of phenolic compounds in fungus, Aspergillus luchuensis.

Abstract: Vanillin is valuable and popular flavor used in foods and cosmetics. Many bacteria species have the ability to decarboxylate substituted cinnamic acids in order to form vanillin. However, the phenolic biotransformation including vanillin production in a common fungus, the Aspergillus luchuensis, which is used in distilled beverages, has not yet been clarified. This study focused on elucidating the vanillin production due to phenolic biotransformation in A. luchuensis during fermentation. The phenolic metabolites were extracted by a solid phase column and they were determined using on LC/MS and LC/MS/MS in a selective ion mode. As a result, ferulic acid, vanillin and vanillic acid, were detected in the rice koji fermentationed by A. luchuensis and also fermentated with yeast. In addition, the accurate molecular formula of vanillin glucoside (C14H17O8, 313.0927, (M-H)− and its production ions was also determined by HRESI-mass spectrometry. Based on the results including the phenolic metabolites and related genes found in A. luchuensis genome, this study proposed the vanillin production mechanism due to the side chain cleavage of ferulic acid through Coenzyme A (CoA) and feruloyl-CoA hydratase/lyase, to form vanillin and acetyl-COA. In this study, another possible vanillin production pathway also was proposed due to the neutral hexose hydrolysis of vanillin glucoside. The subsequent dehydrogenation of vanillin produced vanillic acid. In addition, vanillin was detected in the distilled alcohol indicating its contribution to the aroma profile of beverages. It has been unknown that the vanillin in the distilled solution is derived from the vanillin produced during rice-koji and/or moromi mash fermentations.

Structural and Functional Analysis of UGT92G6 Suggests an Evolutionary Link Between Mono- and Disaccharide Glycoside-Forming Transferases

Abstract: Glycosylation mediated by UDP-dependent glycosyltransferase (UGT) is one of the most common reactions for the biosynthesis of small molecule glycosides. As glycosides have various biological roles, we characterized UGT genes from grapevine (Vitis vinifera). In silico analysis of VvUGT genes that were highly expressed in leaves identified UGT92G6 which showed sequence similarity to both monosaccharide and disaccharide glucoside-forming transferases. The recombinant UGT92G6 glucosylated phenolics, among them caffeic acid, carvacrol, eugenol and raspberry ketone, and also accepted geranyl glucoside and citronellyl glucoside. Thus, UGT92G6 formed mono- and diglucosides in vitro from distinct compounds. The enzyme specificity constant Vmax/Km ratios indicated that UGT92G6 exhibited the highest specificity towards caffeic acid, producing almost equal amounts of the 3- and 4-O-glucoside. Transient overexpression of UGT92G6 in Nicotiana benthamiana leaves confirmed the production of caffeoyl glucoside; however, the level of geranyl diglucoside was not elevated upon overexpression of UGT92G6, even after co-expression of genes encoding geraniol synthase and geraniol UGT to provide sufficient precursor. Comparative sequence and 3-D structure analysis identified a sequence motif characteristic for monoglucoside-forming UGTs in UGT92G6, suggesting an evolutionary link between mono- and disaccharide glycoside UGTs. Thus, UGT92G6 functions as a mono- and diglucosyltransferase in vitro, but acts as a caffeoyl glucoside UGT in N. benthamiana.

Chemical constituents from Canarium album Raeusch and their anti-influenza A virus activities

Abstract: Two new dyhydrophaseic acid glucoside isomers, (1'S, 3'R, 5'S, 8'R, 2Z, 4E)-dihydrophaseic acid-3'-O-β-D-glucopyranoside (2) and (1'R, 3'S, 5'R, 8'R, 2Z, 4E)-dihydrophaseic acid-3'-O-β-D-glucopyranoside (4), together with 10 known compounds [myo-inositol (1), 3,4-dihydroxybenzoic acid (3), 3-O-galloyl quinic acid (5), ellagic acid (6), gallic acid (7), ethyl gallate (8), scopoletin (9), ellagic acid-4-O-β-D-glucopyranoside (10), ellagic acid-4-O-α-L-rhamnopyranoside (11), and isocorilagin (12)] were isolated from the chloroform extract of Canarium album Raeusch fruits by repeated chromatography on macroporous adsorption resin, silica gel, Sephadex LH-20, Toyopearl HW-40F, and reverse-phase C18 columns, etc. Their structures and absolute configurations were determined by comprehensive analysis of 1D- and 2D-nuclear magnetic resonance (NMR), high-resolution electron spray ionization mass spectrometry (HR-ESI-MS), ESI-MS, optical rotation, circular dichroism spectra, and comparison of NMR data with data of known compounds. Bioassay of their anti-influenza virus A activities showed that compounds 9 and 12 displayed a significant inhibitory effect with IC50 values of 22.9 ± 3.7 and 5.42 ± 0.97 μg/ml, respectively.

Glucosylation of T-2 and HT-2 toxins using biotransformation and chemical synthesis: Preparation, stereochemistry, and stability

Abstract: Plant-derived phase II metabolites of T-2 toxin (T2) and HT-2 toxin (HT2) were first described in 2011 and further characterized in the following years. Since then, some efforts have been made to understand their biosynthesis, occurrence, toxicity, toxicokinetics, and finally relevance for consumers. Thus, the probably most important question is whether and how these metabolites contribute to toxicity upon hydrolysis either during food processing or the gastrointestinal passage. To answer this question, firstly, knowledge on the correct stereochemistry of T2 and HT2 glucosides is important as this affects hydrolysis and chemical behavior. So far, contradictory results have been published concerning the number and anomericity of occurring glucosides. For this reason, we set up different strategies for the synthesis of mg-amounts of T2, HT2, and T2 triol glucosides in both α and s configuration. All synthesized glucosides were fully characterized by NMR spectroscopy as well as mass spectrometry and used as references for the analysis of naturally contaminated food samples to validate or invalidate their natural occurrence. Generally, 3-O-glucosylation was observed with two anomers of HT2 glucoside being present in contaminated oats. In contrast, only one anomer of T2 glucoside was found. The second aspect of this study addresses the stability of the glucosides during thermal food processing. Oat flour was artificially contaminated with T2 and HT2 glucosides individually and extruded at varying initial moisture content and temperature. All four glucosides appear to be more stable during food extrusion than the parent compounds with the glucosidic bond not being hydrolyzed.

Dihydrochalcone Glucosides from the Subaerial Parts of Thonningia sanguinea and Their in Vitro PTP1B Inhibitory Activities.

Abstract: Six new and four known dihydrochalcone glucoside derivatives (1-10), the phenylpropanoid coniferin (11), and the lignans (+)-pinoresinol (12) and lariciresinol (13) were isolated from the subaerial plant parts of Thonningia sanguinea in the course of a screening campaign for new antidiabetic lead compounds The structures of the new substances were elucidated by HRESIMS, NMR, GC-MS, and ECD data evaluation 2'- O-(3-Galloyl-4,6- O- Sa-hexahydroxydiphenoyl-β-d-glucopyranosyl)-3-hydroxyphloretin (4), 2'- O-(4,6- O- Sa-hexahydroxydiphenoyl-β-d-glucopyranosyl)phloretin (5), 2'- O-(3- O-galloyl-4,6- O- Sa-hexahydroxydiphenoyl-β-d-glucopyranosyl)phloretin (6), and thonningianin B (9) showed moderate protein tyrosine phosphatase-1B inhibition in an enzyme assay (IC50 values ranging from 19 to 25 μM), whereas thonningianin A (10) was identified as a more potent inhibitor (IC50 = 44 μM) The observed activity differences could be explained by molecular docking experiments The activity of 10 could further be confirmed in HEPG2 liver carcinoma cells, where the compound was able to increase the level of phosphorylated insulin receptors in a concentration-dependent manner

A New Benzophenone C-Glucoside and Other Constituents of Pseuduvaria fragrans and Their α-Glucosidase Inhibitory Activity

Abstract: Phytochemical investigations of the leaves and stems of Pseuduvaria fragrans led to the isolation of a new benzophenone C-glucoside named pseuduvarioside (1), together with six known compounds including (-)-guaiol (2), (+)-isocorydine (3), cyathocaline (4), isoursoline (5), N-trans-coumaroyltyramine (6), and N-trans-feruloyltyramine (7). Their structures were characterized by NMR spectroscopy and mass spectrometry. All of the isolates were evaluated for inhibitory activity against the enzyme α-glucosidase. N-trans-coumaroyltyramine and N-trans-feruloyltyramine showed higher activity than the drug acarbose. Kinetic studies revealed that both tyramine-derived amides were uncompetitive inhibitors of the enzyme.

A Novel Flavonoid Glucoside from the Fruits of Lycium ruthenicun

Abstract: A novel flavonoid glucoside, ruthenicunoid A (1), together with eight known substances, were isolated from the fruits of Lycium ruthenicun Murr. Their structures were elucidated by extensive spectroscopic data and chemical methods. Especially, the absolute configuration of glucose residue in 1 was assigned by acid hydrolysis followed by derivatization and GC analysis. Biological evaluation towards Sirtuin 1 (SIRT1) found that compounds 1 and 2 exhibit inhibitory activity against SIRT1 in a concentration-dependent manner, indicating its potential on SIRT1-associated disorders.

Cytotoxic and anti-inflammatory compounds from Red Sea grass Thalassodendron ciliatum

Abstract: Chemical investigation of the less polar fraction methylene dichloride–methanol extract of the Red Sea grass Thalassodendron ciliatum led to the isolation of a new phytoceramide molecular species TCC-1, along with four known compounds: 7β-hydroxy cholesterol (10), 7β-hydroxysitosterol (11), stigmasterol glucoside (12), and β-sitosterol glucoside (13). Phytosphingosines with 2-hydroxy fatty acid residues constituted the phytoceramide molecular species TCC-1. Further purification of TCC-1 afforded two new phytoceramides: TCC-1-5 (5) and TCC-1-7 (7) as well as the known ceramide TCC-1-6 (6). All compounds are reported for the first time from this genus. The chemical structures of the isolated compounds were clarified on the basis of spectroscopic techniques including IR, NMR experiments, mass spectrometry, and chemical methods, in addition to comparison with literature data. All isolated compounds exhibited significant cytotoxicity against two human cell lines (Hep G2 and MCF-7). Moreover, compounds (10–13) have been found to possess significant anti-inflammatory activity in which compound (13) is the most potent.

Bioconversion of Tetracycline Antibiotics to Novel Glucoside Derivatives by Single-Vessel Multienzymatic Glycosylation.

Abstract: The single-vessel multienzyme UDP-α-D-glucose recycling system was coupled with a forward glucosylation reaction to produce novel glucose moiety-conjugated derivatives of different tetracycline antibiotic analogs. Among five tetracycline analogs used for the reaction, four molecules (chlorotetracycline, doxytetracycline, meclotetracycline, and minotetracycline) were accepted by a glycosyltransferase enzyme, YjiC, from Bacillus licheniformis to produce glucoside derivatives. However, the enzyme was unable to conjugate sugar units to rolitetracycline. All glucosides of tetracycline derivatives were characterized by ultraviolet absorbance maxima, ultra-pressure liquid chromatography coupled with photodiode array, and high-resolution quadruple time-of-flight electrospray mass spectrometry analyses. These synthesized glucosides are novel tetracycline derivatives.

HPLC-ESI-MS/MS characterization of phenolics in prunus amygdalus, cultivar “umm alfahm” and its antioxidant and hepatoprotective activity

Abstract: Metabolite profiling of the total ethanolic extract of Prunus amygdalus stem and leaves was carried out for the first time using LC-DAD-ESI-MS in the negative ion mode to investigate its chemical composition. Results revealed the identification of 33 phenolic compounds. Fifteen compounds were investigated in P. amygdalus for the first time and identified as; veratic acid, rosmarinicacid, protocatechuic acid-hexoside, 3-O-caffeoylquinic acid (neochlorogenic acid), dihydroquercetin- hexoside, coumaroyl-quinic acid, vanillic acid glucoside, cis piceid, hesperidin, dihydrokaempferol, acteoside, quercetin acetyl hexoside, homovanillic acid, fisetin-deoxyhexoside. The antioxidant potential of the total ethanolic extract (EE) and the fractions: petroleum ether (PE), chloroform (CE), ethyl acetate (EtE), methanol eluted diaion (DME) and diaion eluted with 50% methanol (D 50%E) was performed using DPPH assay. The most potent antioxidant EE, EtE and D50%E extracts (compared with vitamin C) were selected for further hepatoprotective assessment against hepatotoxicity induced by thioacetamide in a dose of 200 mg/kg compared with silymarin (50 mg/kg) as a standard drug. Results revealed the significant reversal of the deleterious effects of thioacetamide on serum ALT, AST and total protein in the order: EtE > (Silymarin = EE) > D50% E. The biochemical results were corroborated with the histological studies of liver.

Terpenoids from Vitex trifolia and their anti-inflammatory activities

Abstract: A new diterpenoid glucoside, (3S,5S,6S,8R,9R,10S)-3,6,9-trihydroxy-13(14)-labdean-16,15-olide 3-O-β-D-glucopyranoside (1), and a new iridoid glucoside, (1S, 5S,6R,9R)-10-O-p-hydroxybenzoyl-5,6β-dihydroxy iridoid 1-O-β-D-glucopyranoside (2), along with six known compounds (3-8) were isolated from Vitex trifolia L.. Their structures were elucidated by extensive spectroscopic analysis. All these isolated compounds were evaluated for their inhibitory effects on nitric oxide production in LPS-induced RAW 264.7 macrophages. Compounds 2, 4, 5, and 7 showed moderate inhibitory activities with IC50 values of 90.05, 88.51, 87.26, and 76.06 μM, respectively.

Palmitoyl ascorbic acid 2-glucoside has the potential to protect mammalian cells from high-LET carbon-ion radiation

Abstract: DMSO, glycerol, and ascorbic acid (AA) are used in pharmaceuticals and known to display radioprotective effects The present study investigates radioprotective properties of novel glyceryl glucoside, ascorbic acid 2-glucoside, glyceryl ascorbate, and palmitoyl ascorbic acid 2-glucoside (PA) Gamma-rays or high-LET carbon-ions were irradiated in the presence of tested chemicals Lambda DNA damage, cell survival, and micronuclei formation of CHO cells were analyzed to evaluate radioprotective properties Radiation-induced Lambda DNA damage was reduced with chemical pre-treatment in a concentration-dependent manner This confirmed tested chemicals were radical scavengers For gamma-irradiation, enhanced cell survival and reduction of micronuclei formation were observed for all chemicals For carbon-ion irradiation, DMSO, glycerol, and PA displayed radioprotection for cell survival Based on cell survival curves, protection levels by PA were confirmed and comparable between gamma-rays and high-LET carbon-ions Micronuclei formation was only decreased with AA and a high concentration of glycerol treatment, and not decreased with PA treatment This suggests that mechanisms of protection against high-LET carbon-ions by PA can differ from normal radical scavenging effects that protect DNA from damage

Two Novel Proline-Containing Catechin Glucoside from Water-Soluble Extract of Codonopsis pilosula.

Abstract: Choushenflavonoids A (1) and B (2), two unusual proline-containing catechin glucosides, were isolated from the roots of Codonopsis pilosula cultivated in a high-altitude location of Yunnan province. Their structures were determined by spectroscopic data and chemical methods. Specifically, the absolute configuration of glucose residue in 1 and 2 was assigned by acid hydrolysis followed by derivatization and gas chromatography (GC) analysis. In addition, biological evaluation of 1 and 2 against Sirtuin 1 (SIRT1) was carried out.

Biosynthesis of novel 7,8-dihydroxyflavone glycoside derivatives and in silico study of their effects on BACE1 inhibition

Abstract: 7,8-Dihydroxyflavone (7,8-DHF) has been conjugated with glucose moiety to produce glucoside derivatives. Three analogues of 7,8-DHF (7-O-β-d-glucosyl-8-hydroxyflavone, 7-hydroxy-8-O-β-d-glucosyl flavone, and 7,8-di-O-β-d-glucosylflavone) have been successfully produced from in vitro reaction using glycosyltransferase of Bacillus licheniformis. Production of these 7,8-DHF derivatives were shifted to cheaper and easier approach in this study by using engineered Escherichia coli BL21 (DE3) ΔpgiΔzwfΔushA cells in which the flow of glucose-6-phospahte toward glycolysis and pentose phosphate pathway and hydrolysis of UDP-α-d-glucose were blocked while directing the carbon flux toward UDP-α-d-glucose by overexpressing UDP-α-d-glucose pathway genes. Supplementation of 300 μM of 7,8-DHF to the culture resulted in production of 171 μM of 7-O-β-d-glucosyl-8-hydroxyflavone, 68 μM of 7-hydroxy-8-O-β-d-glucoxyflavone, and 55 μM of 7,8-di-O-β-d-glucoxyflavone in laboratory-scale 3-L fermentor, representing 98% bioconversion of initially fed substrate to respective glucoside derivatives within 48 H. These products were characterized by high-performance liquid chromatography-photodiode array (HPLC-PDA), HPLC-PDA-quadruple time of flight-electron spray ionization mass spectrometry, and nuclear magnetic resonance analyses. These newly synthesized derivatives were found to be able to interact with amino acids of active site of human β-site amyloid precursor protein cleaving β-site amyloid precursor protein cleaving enzyme 1 (BACE1) β-secretase enzyme in in silico studies, thus displaying possible application in cure of Alzheimer's disease.

A Novel Heterodimer of Coumaric Acid Glucosides from the Chinese Fern Polypodium hastatum

Abstract: A novel heterodimer of coumaric acid glucoside, polypodiside (1), together with two known caffeic acid derivatives chlorogenic acid (2) and ethyl chlorogenate (3), has been isolated from the Chinese fern Polypodium hastatum. Their structures were determined by various spectroscopic analysis including MS and 1D and 2D NMR (COSY, HMBC, HSQC).