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Absorption​ of free radicals in the body cannot be done by antioxidant compounds originating from the human body, so exogenous antioxidants are required to help in their natural antioxidant action. Oxidative stress can be caused by an imbalance of free radical inhibitors and the accumulation of free radicals that enter cellular structures. Synthetic antioxidants found in external antioxidants are not the primary choice because they are harmful and carcinogenic. Therefore, using natural ingredients provides a necessary alternative to constructing novel natural antioxidants. Recent studies have highlighted critical analysis and evaluation that flavonoids are a unique class of secondary metabolites found in plants and used in communities as traditional therapeutics with proven bioactivity. This could support new discoveries based on various herbal medicines and in addition, the functional effectiveness of flavonoids as antioxidants against free radicals. In this review, there are several strengths in the discussion. First, the study takes a comprehensive approach by covering various aspects, including the properties and sources of free radicals, oxidative stress in relation to different diseases, antioxidant defense mechanisms, and the specific antioxidant mechanisms of flavonoids. Second, the focus on natural antioxidants, especially flavonoids, and also discussion about clinical applications and human studies, limitations, global perspectives, and future research directions of flavonoids compounds become references in the selection of natural medicines. But, several constraints should be considered when interpreting the findings of this review. First, the discussion about the mechanism of antioxidant compounds is only discussed in general and only takes one example of a compound (flavonoid) that has the potential as an antioxidant. Second, the lack of findings regarding the relationship between several diseases discussed with free radicals. Third, a limited number of studies investigated regarding clinical applications and human studies of some of the diseases discussed. [ABSTRACT FROM AUTHOR]

Along with the increasing resistance of Candida spp. to some antibiotics, it is necessary to find new antifungal drugs, one of which is from the medicinal plant Red Betel (Piper crocatum). The purpose of this research is to isolate antifungal constituents from P. crocatum and evaluate their activities as ergosterol biosynthesis inhibitors via an in silico study of ADMET and drug-likeness analysis. Two new active compounds 1 and 2 and a known compound 3 were isolated, and their structures were determined using spectroscopic methods, while their bioactivities were evaluated via in vitro and in silico studies, respectively. Antifungal compound 3 was the most active compared to 1 and 2 with zone inhibition values of 14.5, 11.9, and 13.0 mm, respectively, at a concentration of 10% w/v, together with MIC/MFC at 0.31/1.2% w/v. Further in silico study demonstrated that compound 3 had a stronger ΔG than the positive control and compounds 1 and 2 with −11.14, −12.78, −12.00, and −6.89 Kcal/mol against ERG1, ERG2, ERG11, and ERG24, respectively, and also that 3 had the best Ki with 6.8 × 10−3, 4 × 10−4, 1.6 × 10−3, and 8.88 μM. On the other hand, an ADMET analysis of 1–3 met five parameters, while 1 had one violation of Ro5. Based on the research data, the promising antifungal constituents of P. crocatum allow P. crocatum to be proposed as a new antifungal candidate to treat and cure infections due to C. albicans. [ABSTRACT FROM AUTHOR]

Glycerol is a symmetrical, small biomolecule with high flexibility in molecular conformations. Using a 1H-NMR spectroscopic Karplus analysis in our way, we analyzed a rotational isomerism in the glycero backbone which generates three kinds of staggered conformers, namely gt (gauche-trans), gg (gauche-gauche), and tg (trans-gauche), at each of sn-1,2 and sn-2,3 positions. The Karplus analysis has disclosed that the three rotamers are consistently equilibrated in water keeping the relation of 'gt:gg:tg = 50:30:20 (%)' at a wide range of concentrations (5 mM~540 mM). The observed relation means that glycerol in water favors those symmetric conformers placing 1,2,3-triol groups in a gauche/gauche geometry. We have found also that the rotational isomerism is remarkably changed when the solvent is replaced with DMSO-d6 or dimethylformamide (DMF-d7). In these solvents, glycerol gives a relation of 'gt:gg:tg = 40:30:30 (%)', which means that a remarkable shift occurs in the equilibrium between gt and tg conformers. By this shift, glycerol turns to also take non-symmetric conformers orienting one of the two vicinal diols in an antiperiplanar geometry. [ABSTRACT FROM AUTHOR]

Herein, o-(methoxycarbonyl)phenyl thioglycosides [or (methyl)salicyl 1-thioglycosides] were evaluated as non-malodorous thioglycoside alternatives. The o-methoxycarbonyl group was expected to assist in the departure of leaving group. Salicyl-type thioglycosides exhibited high reactivity and glycosylation yields when N-iodosuccinimide and trifluoromethanesulfonic acid were used as promoters. Glycosylation with these thioglycosides in dichloromethane showed similar reactivity and stereoselectivity as those of phenyl thioglycosides. Glycosylation with per-O-benzyl salicyl-type thioglycosides in dichloromethane showed 1,2-cis-selectivity, while the same reaction in nitriles afforded predominantly 1,2-trans glycosides. In contrast, glycosylation with per-O-benzoyl thioglycosides afforded exclusively 1,2-trans glycosides. These results strongly suggest that salicyl-type thioglycosides can serve as non-malodorous alternatives for phenyl thioglycosides. [ABSTRACT FROM AUTHOR]

Osteoporosis is associated with increase in fat tissue in bone marrow in humans. Mesenchymal stem cells in bone marrow are induced to differentiate into osteoblasts rather than adipocytes by the stimulation of peroxisome proliferator-activated receptor (PPAR) γ antagonists. PPARγ antagonists are expected to be useful to prevent osteoporosis by regulating the lineages of mesenchymal stem cells in bone marrow, as well as the prevention of obesity. In this study, we explored natural components suppressing PPARγ transcriptional activity in rosemary. Separation of active fraction of rosemary extract by repeated high performance liquid chromatograph and PPARγ luciferase reporter assay identified erucic acid, one of the monounsaturated fatty acids, as an active component. Twenty-five-micrometer erucic acid significantly decreased PPARγ luciferase activity and enhanced the differentiation of mouse-delivered C3H10T1/2 cells into osteoblasts rather than adipocytes. Furthermore, 25-μM erucic acid significantly decreased the expression of adipocyte marker genes, while accelerating osteoblast marker genes. In conclusion, erucic acid is a novel natural component derived from rosemary regulating mesenchymal stem cell differentiation via suppression of PPARγ transcriptional activity. [ABSTRACT FROM AUTHOR]

A facile methodology is proposed for regioselective conjugation between glycosyl donors and acceptors towards the development of regioselective 1,2-cis-glycosylation method.ortho-Formylphenyl 1-thio-β-d-galactopyranoside was regioselectively tethered to methyl α-d-glucopyranoside under acidic condition to furnish an 4,6-O-arylidene acetal-linked conjugate. This conjugate can be readily converted to an ether-linked 4-O- or 6-O-derivative by regioselective cleavage of the acetal ring. In the glycosylation reaction, the ether-linked 4-OH conjugate was found to show excellent 1,2-cisselectivity via an intramolecular 1,9-transfer. [ABSTRACT FROM PUBLISHER]

A new series of salicyl glycoconjugates containing hydrazide and hydrazone moieties were designed and synthesized. The bioassay indicated that the novel compounds had no in vitro fungicidal activity but showed significant in vivo antifungal activity against the tested fungal pathogens. Some compounds even had superior activity than the commercial fungicides in greenhouse trial. The results of RT-PCR analysis showed that the designed salicyl glycoconjugates could induce the expression of LOX1 and Cs-AOS2, which are the specific marker genes of jasmonate signaling pathway, to trigger the plant defense resistance. [ABSTRACT FROM AUTHOR]

The article discusses a study which analyses the effects of modified arabinoxylan obtained from MGN-3 hemicelluloses of rice bran on galactosamine (n-GalN) induced interleukin-18 expression and hepatitis in rats. It reports that MGN-3 and its low molecular weight hydrolysate alleviate n-GalN induced hepatitis in rats. It suggests protective effect of interleukin-18 expression against n-GalN induced liver injury.

The article presents a study on the overproduction and purification of oligoxylosyl transfer enzyme (OxtA)[(H)E], a N-terminally His-tagged recombinant form of OxtA, in Escherichia coli. It notes that the purified OxtA(H)E showed a high transxylosylation activity. Moreover, the deduced amino acid sequence of OxtA(H)E revealed a complete resemblance to xylanases, which belongs to a family 11 of glycosyl hydrolase.

Single-wall carbon nanotubes (SWNTs) can be well-dispersed in water by wrapping with short segments of natural DNA from salmon sperm. We report here the isolated DNA-wrapped SWNT hybrids. Measurements were carried out using UV-vis-NIR, near-infrared photoluminescence (PL) spectrum and atomic force microscopy (AFM). A possible charge transport between SWNTs and salmon-DNA is discussed in terms of observed spectral shifts in the photoluminescence spectra. [ABSTRACT FROM AUTHOR]

Abstract: A new hybrid material C10H2@SWNTs, single-wall carbon nanotubes (SWNTs) encapsulating C10H2 polyyne molecules, has been synthesized and confirmed by Raman spectroscopy and X-ray diffraction measurement. The C10H2 polyyne molecules composed of linearly bonded sp-carbon atoms are aligned inside the SWNTs. This hybrid material exhibits a characteristic Raman signal at 2066cm−1 attributable to the stretching vibration of the C10H2 molecules interacting with SWNTs. Being trapped inside the SWNTs, the otherwise unstable C10H2 molecules are shown to be stable well above 300°C under dry-air conditions. [Copyright &y& Elsevier]

Studies the chemical structure and immunogenic activity of alpha-D-glucopyranosyl-sn-glycerophospholipids isolated from Mycoplasma fermentans. Donor synthesis; Bromination reaction.

Lactosides having either an amino-triethylene glycol or an azido-triethylene glycol were designed and synthesized, and the two derivatives were immobilized onto silicon nitride (SiN) surfaces. When a click reaction was applied for the immobilization of the azido-sugar, a Ricinus communis lectin (RCA 120) was detected with a higher response by reflectometric interference spectroscopy (RIfS). When an N -hydroxysuccinimide (NHS) method was applied for the sugar immobilization, the response was less than that of the click one. The response of bovine serum albumin (BSA) as the negative control was negligible, but the lactose-SiN chip prepared by the click method suppressed nonspecific binding more effectively than did the chip from the NHS method. Next, we examined an antibody-immobilized SiN chip prepared by the click reaction. The detection response was, however, lower than that of the lactose-SiN chip, meaning that the sugar-chip by the click reaction was superior to the antibody-chip. Finally, to detect Shiga toxins from Escherichia coli O157:H7, globotrisaccharide (Gb 3) with an azido-triethylene glycol was synthesized and immobilized onto the SiN chip by the click reaction. The Gb 3 -SiN chips enabled us to detect the toxins at concentrations less than 100 ng/mL. RCA 120 , horse gram, gorse lectins and BSA showed no response to the Gb 3 -SiN chip, showing a high specificity for the toxin. Image 1 • Silicon nitride chips were modified with lactose by a click reaction or N -hydroxysuccinimide (NHS) method. • Lactose chips by the click chemistry showed a better sensitivity than those by the NHS method. • Detection response of the antibody-SiN chip was lower than that of the Lac SiN chip. • Shiga toxins were detected at 100 ng/mL with globotrisaccharide chips made by the click reaction. [ABSTRACT FROM AUTHOR]

Abstract: Lipopolysaccharides constitute the outer leaflet of the outer membrane of Gram-negative bacteria and are therefore essential for cell growth and viability. The heptosyltransferase WaaC is a glycosyltransferase (GT) involved in the synthesis of the inner core region of LPS. It catalyzes the addition of the first l-glycero-d-manno-heptose (heptose) molecule to one 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) residue of the Kdo2-lipid A molecule. Heptose is an essential component of the LPS core domain; its absence results in a truncated lipopolysaccharide associated with the deep-rough phenotype causing a greater susceptibility to antibiotic and an attenuated virulence for pathogenic Gram-negative bacteria. Thus, WaaC represents a promising target in antibacterial drug design. Here, we report the structure of WaaC from the Escherichia coli pathogenic strain RS218 alone at 1.9 Å resolution, and in complex with either ADP or the non-cleavable analog ADP-2-deoxy-2-fluoro-heptose of the sugar donor at 2.4 Å resolution. WaaC adopts the GT-B fold in two domains, characteristic of one glycosyltransferase structural superfamily. The comparison of the three different structures shows that WaaC does not undergo a domain rotation, characteristic of the GT-B family, upon substrate binding, but allows the substrate analog and the reaction product to adopt remarkably distinct conformations inside the active site. In addition, both binary complexes offer a close view of the donor subsite and, together with results from site-directed mutagenesis studies, provide evidence for a model of the catalytic mechanism. [Copyright &y& Elsevier]

Cell-membrane glycerolipids exhibit a common structural backbone of asymmetric 1,2-diacyl- sn -glycerol bearing polar head groups in the sn -3 position. In this study, the possible effects of sn -3 head groups on the helical conformational property around the 1,2-diacyl moiety in the solution state were examined. 1 H NMR Karplus relation studies were carried out using a series of 1,2-dipalmitoyl- sn -glycerols bearing different sn -3 substituents (namely palmitoyl, benzyl, hydrogen, and phosphates). The 1 H NMR analysis indicated that the helical property around the 1,2-diacyl moiety is considerably affected by these sn -3 substituents. The sn -3 hydroxy group induced a unique helical property, which was considerably dependent on the solvents used. In CDCl 3 solution, three staggered conformers, namely gt(+), gg(-) and tg, were randomized, while in more polar solvents, the gt(+) conformer with (+)-helicity was amplified at the expense of gg(-) and tg conformers. The sn -3 phosphocholine in phosphatidylcholine exhibited a greater effect on the gt(+) conformer, which was independent of the solvents used. From the 1 H NMR analysis, the helical conformational properties around the 1,2-diacyl moiety conformed to a simple empirical rule, which permitted the proposal of a conformational diagram for 1,2-dipalmitoyl- sn -glycerols in the solution states.

Glycosyl-[60]fullerenes were first used as decontaminants against ricin, a lactose recognition proteotoxin in the Ricinus communis family. A fullerene glycoconjugate carrying two lactose units was synthesized by a [3 + 2] cycloaddition reaction between C60 and the azide group in 6-azidohexyl β-lactoside per-O-acetate. A colloidal aqueous solution with brown color was prepared from deprotected bis(lactosyl)-C60 and was found stable for more than 6 months keeping its red color. Upon mixing with an aqueous solution of Ricinus communis agglutinin (RCA120), the colloidal solution soon caused precipitations, while becoming colorless and transparent. In contrast, a solution of concanavalin A (Con A) caused no apparent change, indicating that the precipitation was caused specifically by carbohydrate-protein interactions. This notable phenomenon was quantified by means of sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and the results were discussed in terms of detection and decontamination of the deadly biological toxin in the Ricinus communis family.

Mycoplasma fermentans possesses unique α-glycolipid antigens (GGPL-I and GGPL-III) at the cytoplasm membrane, which carry a phosphocholine group at the sugar primary (6-OH) position. This paper describes a practical synthetic pathway to a GGPL-I homologue (C(16:0)) and its diastereomer, in which our one-pot α-glycosylation method was effectively applied. The synthetic GGPL-I isomers were characterized with (1)H NMR spectroscopy to determine the equilibrium among the three conformers (gg, gt, tg) at the acyclic glycerol moiety. The natural GGPL-I isomer was found to prefer gt (54%) and gg (39%) conformers around the lipid tail, while adopting all of the three conformers with equal probability around the sugar position. This property was very close to what we have observed with respect to the conformation of phosphatidylcholine (DPPC), suggesting that the Mycoplasma glycolipids GGPLs may constitute the cytoplasm fluid membrane together with ubiquitous phospholipids, without inducing stereochemical stress.

Galacto-trehalose (GT) is a novel class of 1,1'-linked nonreducing disaccharide having an α-galactoside epitope. In this study, a pair of α,α- and α,β-GT isomers were prepared in one pot with our α-glycosylation method, converted into vinyl monomers and then subjected to radical copolymerization with a second sugar (4-acrylamidophemyl β-Glc or β-GlcNAc) in the presence of acrylamide. The derived glycopolymers were assayed with α-galactoside-specific proteins (BSI-B(4) lectin and Shiga toxin-1) to show the results that both α,α- and α,β-isomers are recognized by these carbohydrate-binding proteins more strongly in forms of the GT polymers. Moreover, the glycopolymer carrying both α,α-GT and β-GlcNAc along the polymer chain showed an integrated detoxifying activity to the E. coli toxin as the result of a "module effect" of the second sugar.

Heptosides are found in important bacterial glycolipids such as lipopolysaccharide (LPS), the biosynthesis of which is targeted for the development of novel antibacterial agents. This work describes the synthesis of a fluorinated analogue of ADP-L-glycero-beta-D-manno-heptopyranose, the donor substrate of the heptosyl transferase WaaC, which catalyzes the incorporation of this carbohydrate into LPS. Synthetically, the key step for the preparation of ADP-2F-heptose is the simultaneous and stereoselective installation of both the fluorine atom at C-2 and the phosphoryl group at C-1 through a selectfluor-mediated (selectfluor=1-chloromethyl-4-fluorodiazoniabicyclo[2.2.2]octane bis(triflate)) electrophilic addition/nucleophilic substitution involving a heptosylglycal. Therefore, we detail in this article 1) the stereoselective preparation of the key intermediates heptosylglycals, 2) the development of a new fluorophosphorylation procedure allowing an excellent beta-gluco stereoselectivity with "all-equatorial" glycals, 3) the synthesis of the target ADP-2F-heptose, and 4) some comments on the contacts observed between the fluorine atom of the final molecule and the protein in the crystallographic structure of heptosyltransferase WaaC.

Shiga toxin (Stx) is one of the most critical factors in the development of hemolytic uremic syndrome and other systemic complications following enterohemorrhagic Escherichia coli (EHEC) infection. Substances neutralizing Stx by interfering with toxin-receptor binding have been explored as therapeutic candidates for EHEC infection. In this study, we examined globotriaosyl (Gb3), galabiosyl (Gb2) and galacto-trehalose, each of which was synthetically conjugated with a polyacrylamide backbone, for Stxneutralizing activity. Galacto-trehalose was designed as a Gb2 mimicking, unnatural Stx-ligand that was expected to show tolerance to enzymatic degradation in vivo. Galacto-trehalose copolymer showed neutralizing activity against Stx-1 but not Stx-2 in a HeLa cell cytotoxicity assay. It was thought that galactotrehalose copolymer could be a lead compound for the treatment of Stx-mediated diseases, although it requires modification to show neutralizing activity to Stx-2. The Gb3 copolymer with high sugar unit density showed stronger neutralizing activity against Stx-2 than those with lower density. However, the density-dependency of the neutralizing activity was less obvious against Stx-1. Intravenous administration of the Gb3 copolymer prevented death in mice lethally infected with Stx-1- and Stx-2-producing E. coli O157:H7. Thus, we demonstrated that the artificial Gb3 copolymer could neutralize Stx-1 and the more clinically relevant Stx-2 in vitro and effectively inhibit Stx toxicity in vivo.

Fluorinated carbohydrates constitute a very important class of mechanistic probes for glycosyl-processing enzymes. In this study, we describe the first synthesis of fluorinated and phosphonylated exo-glycals and their corresponding nucleotide sugars in the galactofuranose series. The synthetic protocol that we have developed is a Selectfluor-mediated fluorination/elimination sequence on phosphonylated exo-glycals, and it offers a new entry into fluorinated carbohydrate chemistry. The challenging E/Z stereochemical assignment of the resulting tetrasubstituted alkenes, which bear an alkoxy, an alkyl, a fluoro, and a phosphonyl group, has been achieved through NMR experiments. The corresponding (E)- and (Z)-nucleotide fluorosugars have been prepared and tested as inhibitors of UDP-galactopyranose mutase (UGM). UGM is a flavoenzyme that catalyzes the isomerization of uridine diphosphate(UDP)-galactopyranose into UDP-galactofuranose, a key step of the biosynthesis of important mycobacterial cell-wall glycoconjugates. The two diastereomeric molecules were found to display time-dependent inactivation of UGM, as expected from preliminary results using non-fluorinated exo-glycal nucleotides. The inhibitory properties of the two fluorinated molecules led us to suggest that the inactivation mechanism proceeds through two-electron processes, despite the presence of the flavin cofactor within the UGM catalytic site.

The reaction of a 2-O-benzyl-1-hydroxy sugar with CBr4 and Ph3P generates a glycosyl bromide in situ, which is coupled with an acceptor alcohol in the presence of N,N-tetramethylurea to afford an alpha-glycosyl product virtually quantitatively. In a proposed pathway, the reagent combination plays multiple roles such as the generation of a glycosyl donor, the activation of glycosylation, and the dehydration of the reaction system. These roles allow a simple alpha-glycosylation to be performed without special attention to dehydration. Various alpha-glycosyl (D-gluco-, D-galacto- and L-fuco-) products including glycosyl glycerols and cholesterols have been prepared with this method.

[reaction: see text] A concept for the development of practical glycosylation is presented and demonstrated by one-pot alpha-glycosylation applying Appel agents for 2-O-benzyl-1-OH hexoses in DMF. The reaction, in situ giving the equilibrium of glycosyl bromides and more reactive O-glycoside intermediates, accomplishes a near-quantitative alpha-glycosylation removing the water molecules.

A simple globobiosyl (Gb2) ceramide mimic carrying a monoalkyl chain (C18) was applied for a monolayer Langmuir-Blodgett (L-B) technique to detect Shiga toxins (Stxs) by a quartz crystal microbalance (QCM) method. The artificial glycolipid, synthesized from penta-O-acetyl-D-galactopyranose via a conventional glycosidation pathway, was developed at the air-water surface for the formation of the monolayer film. Then, the film was transferred onto a QCM cell surface modified with alkanethiols. Upon the addition of each of Stx-1 and Stx-2, the decrease of frequency reached saturation within 45 min at a few nanogram order per quartz cell. Binding constants (Ka) estimated for each of Stx-1 and Stx-2 showed little difference between the two toxins. On the other hand, in the presence of an artificial acrylamido Gb2 copolymer as a competitive inhibitor, the two toxins showed a large difference in the binding behavior to the L-B monolayer.

Galacto-type trehalose, a "C-4 epimer of trehalose", possesses a stereochemical structure around the alpha(1-1)-linkage analogous to that of the globobiosyl alpha(1-4)-linkage in Gb(2) and Gb(3) ceramides, which are known as the ligands of Shiga toxins produced by pathogenic E. coli. This paper presents evidence supporting the new idea of using a trehalosyl alpha(1-1)-linkage as a substitute for the galactobiosyl alpha(1-4)-linkage.